fHANOI UNIVERSITY OF SCIENCE AND TECHNOLOGY

SCHOOL OF CHEMICAL ENGINEERING

Dept. of Pharmaceutical Chemistry and Pesticides Technology

---------------o0o---------------

DESCRIPTION

BACHELOR’S THESIS
“Experimental research and design calculations for the production system
of Carboxymethyl Cellulose pharmaceuticals from cotton with a capacity of
1000 tons/year”

Supervisor : Assoc.Prof. Ta Hong Duc

Student : Nguyen Thu Tra
Student ID : 20191378
Class : Advance program of Pharmaeutical
Engineering – K64
 HANOI UNIVERSITY OF SCIENCE AND TECHNOLOGY

GRADUATION THESIS

Experimental research and design calculations for the

production system of carboxymethyl cellulose
pharmaceuticals from cotton with a capacity of 1000 tons/year

NGUYEN THU TRA

[email protected]

School of Chemical Engineering

Advanced Program of Pharmaceutical Engineering

Thesis supervisor: Assoc.Prof. Ta Hong Duc

Signature of supervisor

Department: Dept. of Pharmaceutical Chemistry and Pesticides Tech.

Institute: School of Chemiscal Engineering

 BỘ GIÁO DỤC VÀ ĐÀO TẠO CỘNG HÒA XÃ HỘI CHỦ NGHĨA VIỆT NAM
ĐẠI HỌC BÁCH KHOA HÀ NỘI Độc lập – Tự do – Hạnh phúc

GRADUATION THESIS ASSIGNMENT

Student’s name: Nguyen Thu Tra Student ID: 20191378 Cohort: 64

School: School of Chemical Engineering Major: Advance Program of Pharmaceutical Engineering

1. Design title:

“Experimental research and design calculations for the production system of Carboxymethyl
Cellulose pharmaceuticals from cotton with a capacity of 1000 tons/year”

2. Initial data
- Parameters of the technology are determined through experimental research.
- Other data is self-researched by students
- Carboxymethyl Cellulose (CMC) production system with a capacity of 1000 tons
per year
3. Requirements for presentation and calculation
- Research to determine the technological conditions for conducting the CMC
synthesis reaction.
- Establish the CMC production process: create a block diagram, P&ID diagram,
and design reaction equipment.
4. Requirements for presenting the drawings
- PFD drawings (size A0)
- P&ID drawing (size A0)
- GA drawing for main equipment (size A1)
5. Other requirements: Complete the project on schedule
6. Project assignment date: November 10, 2022
7. Project completion date: August 1, 2023

November 10, 2022

Supervisor
 TABLE OF CONTENTS

LIST OF FIGURES AND CHARTS ...............................................................................1

LIST OF TABLES ...........................................................................................................2
LIST OF ABBREVIATIONS ..........................................................................................4
LỜI CẢM ƠN ..................................................................................................................5
ACKNOWLEDGEMENT ...............................................................................................6
INTRODUCTION ...........................................................................................................7
CHAPTER 1 ....................................................................................................................9
OVERVIEW ....................................................................................................................9
1.1. COTTON ............................................................................................................9
1.1.1. Scientific name ......................................................................................9
1.1.2. History [6] ...............................................................................................9
1.1.3. Botanical characteristic [6] ...................................................................10
1.1.4. Distribution and ecology .....................................................................10
1.1.5. Chemical compositions ....................................................................... 11
1.2. CARBOXYMETHYL CELLULOSE ..............................................................13
1.2.1. Definition.............................................................................................13
1.2.2. Classification .......................................................................................14
1.2.3. Classification by application ...............................................................15
1.2.4. Typycal properties ...............................................................................16
1.2.5. Stability and Storage Conditions [5] .....................................................17
1.2.6. Incompatibilities ..................................................................................18
1.2.7. Safety ...................................................................................................18
1.2.8. Synthesis of Sodium carboxymethyl cellulose pharmaceutical grade 19
CHAPTER 2 ..................................................................................................................22
MATERIALS AND RESEARCH METHODS .............................................................22
2.1. MATERIALS ....................................................................................................22
2.1.1. Cotton ..................................................................................................22
2.1.2. Sodium hydroxide (NaOH) .................................................................24
2.1.3. Isopropanol (IPA) ................................................................................24
2.1.4. Monochloroacetic acid (MCA) ...........................................................25
2.1.5. Acid acetic (CH3COOH) .....................................................................26
 2.1.6. Ethanol (EtOH) ...................................................................................26
2.2. RESEACH METHODS ...................................................................................28
2.2.1. Methodology for studying the technological conditions of the reaction
to produce Na-CMC. ........................................................................................28
2.2.2. Methodology for studying the purification process of Na-CMC. .......31
2.2.3. Analysis method ..................................................................................31
CHAPTER 3 ..................................................................................................................37
RESULTS AND DISCUSSIONS ..................................................................................37
3.1. RESULTS OF THE EXPERIMENT TO DETERMINE THE REACTION
TECHNOLOGY CONDITIONS FOR NA-CMC PRODUCTION .........................37
3.1.1. Investigate the effect of NaOH concentration .....................................37
3.1.2. Investigate the effect of molar ratio MCA/AGU ................................40
3.1.3. Investigate the effect of molar ratio NaOH/MCA ...............................42
3.2. RESULTS OF THE EXPERIMENT TO DETERMINE PURIFICATION
CONDITIONS FOR NA-CMC PRODUCTION ......................................................43
3.2.1. Investigate the effect of washing solvent on Na-CMC purity.............43
3.2.2. Effect of washing times and washing volume on Na-CMC purity .....45
3.3. CONCLUSIONS ..............................................................................................46
CHAPTER 4 ..................................................................................................................47
CALCULATION AND DESIGN OF THE NA-CMC PRODUCTION
TECHNOLOGY PROCESS..........................................................................................47
4.1. BASIS OF CALCULATION............................................................................47
4.1.1. Calculation of the composition of the mixture after the reaction .......47
4.1.2. The overall yield of the entire system .................................................49
4.1.3. Na-CMC production process ...............................................................49
4.1.4. The Process Flowing Diagram (PFD) .................................................50
4.1.5. The Process and Instrumentation Diagram streamchart (P&ID). .......50
4.1.6. Diagram illutration ..............................................................................50
4.1.7. Materials balance.................................................................................53
4.2. CALCULATE FOR THE EQUIPMENT OF NA-CMC SYNTHESIS
PROCESS .................................................................................................................67
4.2.1. Heat balances .......................................................................................67
4.2.2. Detailed calculation of Na-CMC synthesis reactor .............................72
4.3. GENERAL ARRANGEMENT DRAWING FOR ETHERIFICATION
REACTOR ................................................................................................................87
CONCLUSIONS ...........................................................................................................88
REFERENCE ................................................................................................................89
APPENDIX 1 ................................................................................................................92
OCCUPATIONAL HEALTH AND SAFETY AND ENVIRONMENT .......................92
APPENDIX 2 ..............................................................................................................102
PROCESS DIAGRAM AND EQUIPMENT DESIGN DRAWINGS ........................102
 LIST OF FIGURES AND CHARTS

Figure 1.1. Cellulose structure.......................................................................................12

Figure 1.2. The positions on glucose units where the carboxymethyl group is
substituted ......................................................................................................................13
Figure 1.3. Structure of Sodium Carboxymethyl Cellulose (Na-CMC) .......................14
Figure 1.4. Alkalization of Cellulose in NaOH solution ...............................................19
Figure 1.5. Etherification of alkali cellulose to obtain Sodium carboxymethyl cellulose
.......................................................................................................................................20
Figure 1.6. Side reaction between Na-MCA and NaOH to create Sodium Glycolate ..20
Figure 2.1. Reaction between Na-CMC and HNO3 ......................................................32
Figure 2.2. A calibration curve for colorimetric determination of glycolic acid with the
2,7-dihydroxynaphthalene reagent ................................................................................35
Figure 3.1. The change of DS with different concentrations of NaOH.........................38
Figure 3.2. Sample product image NC1, almost no reaction occurs so the product looks
like the original cotton. ..................................................................................................39
Figure 3.3. Results when dissolving sample NC7 in water ...........................................40
Figure 3.4. The change of DS with different mole ratio MCA/AGU............................41
Figure 3.5. Sample MA4 was clumped due to water absorption during purification ...41
Figure 3.5. The change of DS with different mole ratio NaOH/MCA ..........................43
Figure 3.6. Cloudy filtrate when using washing solvents of 75% (left) and 70% (right)
.......................................................................................................................................44
Figure 4.1. Block diagram of Na-CMC production process .........................................50
Figure 4.2. Simulation results of EtOH recovery using Aspen Plus V11......................61
Figure 4.3. RADFRAC equipment of EtOH recovery process .....................................61

1
 LIST OF TABLES

Table 1.1. Chemical composition of cotton fiber [1] ...................................................... 11

Table 1.2. Viscosity of aqueous carboxymethylcellulose sodium 1% w/v solutions.
(Measurements made with a Brookfield LVT viscometer at 25°C.) [5] .........................14
Table 1.3. Pharmacopeial specifications for carboxymethylcellulose sodium [5]..........16
Table 3.1. Study of the Influence of NaOH Concentration ...........................................37
Table 3.2. Sample analysis results in investigating the effect of NaOH concentration 37
Table 3.3. Study of the Influence of MCA/AGU ratio (mol/mol) .................................40
Table 3.4. Sample analysis results in investigating the effect of MCA/AGU ratio
(mol/mol) .......................................................................................................................40
Table 3.5. Study of the Influence of NaOH/MCA ratio (mol/mol) ...............................42
Table 3.6. Sample analysis results in investigating the effect of NaOH/MCA ratio
(mol/mol) .......................................................................................................................42
Table 3.7. Study of the Influence of EtOH concentration .............................................43
Table 3.8. Sample analysis results in investigating the effect of EtOH concentration..44
Table 3.9. Study of Influence of washing times and washing volume on purity ..........45
Table 3.10. Impurities residue in CMC with various washes ........................................45
Table 4.1. The proportions of substances before the reaction .......................................47
Table 4.2. Properties and composition of the products after the first filtration .............47
Table 4.3. Properties and composition of the products after the drying process ...........48
Table 4.4. Thành phần hỗn hợp sau phản ứng (bỏ qua dung môi) ................................48
Table 4.5. Full composition of the reaction mixture (excluding solvent) .....................56
Table 4.2. Properties and composition of the products after the first filtration .............57
Table 4.6. The material balance table of the Na-CMC production process ..................63
Table 4.6. The material balance table of the Na-CMC production process (continues)63
Table 4.6. The material balance table of the Na-CMC production process (continues)64
Table 4.6. The material balance table of the Na-CMC production process (continues)65
Table 4.6. The material balance table of the Na-CMC production process (continues)65
Table 4.6. The material balance table of the Na-CMC production process (continues)66
Table 4.7. Specific heat capacity of the elements (kJ/kg℃) [18] [20] ...............................68
Table 4.8. Specific heat capacity of the compounds in the synthesis of Na-CMC .......68

2
Table 4.9. The list of input materials for the synthesis of Na-CMC .............................69
Table 4.10. The list of output products of the synthesis reaction of Na-CMC ..............69
Table 4.11. Heat of formation of reactants and product in reaction (2) ........................70
Bảng 4.12. Energies of some chemical bonds [21]..........................................................71
Table 4.13. Heat of formation of reactants and product in reaction (4) ........................71
Table 4.14. The process technology parameters for the reaction equipment ................72
Bảng 4.15. Components of stream 12 ...........................................................................73
Bảng 4.16. Components of stream 11............................................................................74
Bảng 4.17. Components of stream 10 ...........................................................................74
Bảng 4.18. Components of stream 13 ...........................................................................74
Table 4.19. The composition of the mixture before the reaction...................................76
Table 4.20. Parameters of the support lugs ....................................................................87

3
 LIST OF ABBREVIATIONS

CMC Carboxymethyl Cellulose

Na-CMC Sodium Carboxymethyl Cellulose

IPA Isopropanol

HNa Sodium Glycolate

DS Degree of Substitution

4
 LỜI CẢM ƠN

Lời đầu tiên con xin gửi lời cảm ơn tới gia đình, đặc biệt là bà, mẹ và dì đã luôn ở bên
cạnh ủng hộ và yêu thương con trong suốt 4 năm vừa qua để con có đủ điều kiện và tự
tin hoàn thành chương trình học tại Đại học Bách khoa Hà Nội. Con biết sắp tới đây là
khoảng thời gian khó khăn với con khi phải đứng trước nhiều lựa chọn và ngã rẽ, nhưng
con biết dù đi đâu con cũng sẽ có một nơi để về.

Em xin gửi cảm ơn đến PGS. TS. Tạ Hồng Đức, người thầy đã đồng hành và định hướng
cho em từ những ngày đầu tiên. Thầy không chỉ chỉ dạy kiến thức, truyền đạt kinh
nghiệm mà còn luôn dành cho em những lời khuyên tuyệt vời. Thầy luôn là kim chỉ nam
để em noi theo, trở thành một con người có ích cho cộng đồng và cho đất nước.

Để có thể hoàn thành được đồ án tốt nghiệp này, em xin cảm ơn TS. Nguyễn Thị Việt
Thanh đã dẫn dắt em trong quá trình làm nghiên cứu. Cô đã tạo điều kiện cho em làm
thí nghiệm, quan tâm và giúp đỡ em hoàn thành phần bộ số liệu thực nghiệm, làm tiền
đề cho phần thiết kế của em sau này.

Cuối cùng, em xin được gửi những lời yêu thương và cảm ơn chân thành nhất đến các
thầy cô trong Bộ môn Công nghệ hóa dược và Bảo vệ thực vật, Trường Hóa và Khoa
học Sự sống, Đại học Bách khoa Hà Nội. Các thầy cô đã đồng hành cùng em suốt 4 năm
học này, không chỉ truyền đạt kiến thức mà còn là chỗ dựa tinh thần của em khi khó
khăn và mất định hướng. Đặc biệt em xin được gửi lời cảm ơn đến cô Đinh Thị Phương
Anh đã luôn yêu thương, lắng nghe và bên cạnh em khi em khó khăn nhất.

Trong quá trình thực hiện nhiệm vụ đồ án, không thể tránh khỏi những thiếu sót, em
mong muốn nhận được những đóng góp từ thầy cô để bản đồ án được hoàn thiện hơn.
Em xin chân thành cảm ơn!

Hà Nội, ngày 07 tháng 08 năm 2023

Sinh viên thực hiện

Nguyễn Thu Trà

5
 ACKNOWLEDGEMENT

First of all, I would like to express my gratitude to my family, especially my

grandmother, mother, and aunt, who have always been by my side, supporting and
loving me throughout the past 4 years, enabling me with the conditions and confidence
to successfully complete my studies at the Hanoi University of Science and Technology.
I understand that the upcoming period will be challenging for me as I face numerous
choices and crossroads, but I know that wherever I go, there will always be a place for
me to return to

In order to complete this graduation thesis, I would like to express my gratitude to Dr.
Nguyen Thi Viet Thanh for her guidance throughout the research process. She provided
me with the opportunity to conduct experiments, cared about my progress, and assisted
me in compiling experimental data, which served as the foundation for my design work
later on.

Finally, I would like to send my sincerest love and gratitude to all the professors in the
Department of Pharmaceutical Chemistry and Pesticides Technology, School of
Chemical Engineering, Hanoi University of Science and Technology. These professors
have accompanied me throughout these 4 years of study, not only imparting knowledge
but also being a source of spiritual support during times of difficulty and uncertainty. I
particularly want to express my heartfelt thanks to Dr. Dinh Thi Phuong Anh, who has
always shown love, listened, and stood by me during my toughest moments.

During the process of carrying out this thesis, there may have been shortcomings that I
couldn't avoid. I hope to receive contributions from my professors to further enhance
the completeness of the thesis. I sincerely thank you all for your support and guidance!

Hanoi, August 7th, 2023

Performed by the student,

Nguyen Thu Tra

6
 INTRODUCTION
Cotton, scientifically referred to as Gossypium herbaceum, has been cultivated in
Vietnam for approximately 2000 years. It is a well-known plant among the Vietnamese
people and plays a significant role in the country's economy, particularly in the textile
industry. Cotton is primarily grown in the coastal region of Central South Vietnam, with
a notable concentration in Binh Thuan Province. Comprising mainly of Cellulose
[1]
(around 94%) , cotton stands out as the most commonly used source of cellulose in
various industries. Its abundant cellulose content allows for widespread applications in
[2-4]
the synthesis of cellulose derivatives . Among these derivatives, Carboxymethyl
Cellulose (CMC) holds particular importance. At the molecular level, the major
difference between CMC and cellulose is only some anionic carboxymethyl groups (i.e.,
–CH2COOH) in the CMC structure that replace the hydrogen atoms from some
hydroxyl groups present in the pristine cellulose infrastructure. CMC is one of the most
widely used cellulose derivatives due to its unique properties and versatile applications
in various industries. In fact, CMC is often used as the carboxymethyl cellulose Sodium
(Na-CMC) salt because the salt form has better solubility and is easier to store. Due to
its water-soluble nature, which forms a thick and sticky adhesive solution, CMC finds
extensive usage across diverse industries including food, pharmaceuticals, paper
production, textile, and others. In the pharmaceutical industry, CMC is a commonly used
binder, thickener, and emulsifier in various oral and topical dosage forms, including
tablets, capsules, creams, gels, etc. due to its biocompatible and water-soluble properties
[5]
. However, it is important to note that CMC used in the pharmaceutical industry must
have a purity of up to 99.5% and meet the pharmacopeial standards regarding
composition, pH, moisture content, and other specifications [5].

Despite the numerous excellent applications of CMC in various industries, particularly

in the pharmaceutical sector, the production of CMC in Vietnam remains very limited.
Currently, up to 90% of CMC products in the Vietnamese market are imported from
China and Japan. This heavy reliance on imports has resulted in significantly higher
costs for pharmaceutical-grade CMC compared to other excipients in the pharmaceutical
industry. Recognizing the abundant source of raw materials, such as cotton, in Vietnam
and the necessity for proactive domestic production of pharmaceutical-grade CMC to
foster the development of the pharmaceutical industry, I proposed a project titled

7
"Experimental Research and Design Calculation of a Carboxymethyl Cellulose
Production System for Pharmaceuticals from Cotton with a Capacity of 1000
Tons/Year." In this project, I conducted experimental research to establish the
technological conditions for manufacturing pharmaceutical-grade CMC, with laboratory
findings serving as the scientific basis for designing the pharmaceutical-grade CMC
production process.

8
 CHAPTER 1

OVERVIEW
1.1. COTTON
1.1.1. Scientific name

Cotton, scientifically known as Gossypium herbaceum, belongs to the genus Gossypium

and the family Malvaceae. Gossypium herbaceum is also commonly known as Asian
cotton. The genus name Gossypium is derived from the Arabic word "goz," meaning
soft substance, which aligns with the general characteristics of the genus and specifically
with cotton.

1.1.2. History [6]

Species within the genus Gossypium, particularly cotton, are among the most significant
fiber-producing plants globally. The Gossypium genus comprises approximately 50
species, but only a few are commercially cultivated for their fiber. Cotton has been
cultivated and utilized by humans for thousands of years, with evidence of its usage
dating back to ancient civilizations in Egypt, India, and the Americas. In Vietnam, cotton
has been cultivated for over 2000 years. Throughout history, cotton has played a crucial
role in shaping economies and societies. The demand for cotton fibers led to the
establishment of extensive trade routes and the development of the cotton industry
during the Industrial Revolution. Eli Whitney's invention of the cotton gin in the late
18th century revolutionized cotton processing, significantly increasing its production
and making it more economically viable. Cotton has since become a fundamental crop,
driving economic growth and fostering social change worldwide.

Indeed, cotton cultivation has not been without controversy. The historical reliance of
the cotton industry on slave labor in the United States and other regions has left a dark
legacy. Additionally, traditional cotton farming has faced environmental challenges due
to the heavy use of water, pesticides, and fertilizers. In recent years, there has been a
growing movement towards sustainable and organic cotton farming practices to reduce
environmental impact and promote ethical standards in cotton production.

Today, cotton remains a vital commodity in international trade, with major cotton-
producing countries including China, India, the United States, Pakistan, and Brazil. It
continues to be a significant raw material for the textile and fashion industries, while

9
research and development efforts are ongoing to improve cotton varieties, enhance
productivity, and address sustainability concerns. The enduring importance of cotton in
agriculture, commerce, and culture ensures that it will remain a foundational crop for
human society worldwide in the years to come.

In Vietnam, cotton is a raw material used in many industries, especially the textile
industry, contributing up to 15% of the country's GDP. However, the cotton grown and
harvested in Vietnam is just enough to meet domestic demand. Therefore, most cotton
on the Vietnamese market is imported cotton. In the 2019/2020 cycle, Vietnam produced
0.1 thousand metric tons of cotton but imported 597 thoundsand metric tons, and also
exported about 240 thounsans metric tons of cotton.

1.1.3. Botanical characteristic [6]

Gossypium herbaceum exhibits distinct botanical characteristics that set it apart as an
essential cotton species. Its streamers are impressive, large, and bell-shaped, with a
diameter of 3-5 cm and can be found in vibrant colors like yellow, cream, pink, or purple,
depending on the variety. These streamers bear both male and female reproductive parts,
boasting well-developed stamens and pistils. The leaves of Gossypium herbaceum are
equally noteworthy, featuring a broad, hand-like shape with palmately lobed margins
radiating from a central point. Arranged alternately along the soft, non-woody green
stem, which reaches a height of 1 to 2 meters, these leaves display a slightly fuzzy
texture due to fine trichomes on their surface. Beneath the soil, the plant's fibrous root
system spreads extensively, anchoring it securely and facilitating efficient water and
nutrient absorption. After successful pollination, the streamers mature into rounded
capsules known as bolls, approximately 2-3 cm in diameter and enveloped in a dense
layer of short, soft hairs. Each boll shelters numerous small, oval-shaped, dark-colored
seeds embedded within the surrounding white cotton fibers. While Gossypium
herbaceum's cotton fibers are relatively short, measuring around 1 to 2 cm in staple
length, they are utilized in various textile applications, particularly in coarser fabrics and
non-woven products, contributing to the species' continued significance in the cotton
industry.

1.1.4. Distribution and ecology

In its natural habitat, Gossypium herbaceum is well-adapted to the warm and tropical
climate of its native regions. It thrives in areas with abundant sunlight, moderate rainfall,

10
and well-drained soils. The plant's fibrous root system allows it to access water and
nutrients efficiently, making it resilient in varying soil conditions [6]. In Vietnam, cotton
is mainly grown in tropical and subtropical climates, mainly concentrated in the southern
and central provinces of the country. Cotton growing areas usually have an average
temperature of 20-30°C a year, favorable conditions for cotton plants to grow and
develop. In particular, rainfall should be sufficient and regular during the cotton seed
formation period. The soils suitable for cotton cultivation are clay, sandy loam, and
alluvial soil in the Mekong Delta, with good drainage and rich in nutrients. Cotton
planting time is at the end of the rainy season and the beginning of the dry season, from
November to January, taking advantage of the regular rain and sunshine cycle, creating
favorable conditions for the plant to grow.

In terms of ecology, Gossypium herbaceum, like other cotton species, plays a role in
supporting biodiversity. Its streamers attract pollinators like bees and butterflies,
contributing to the ecosystem's overall health and functioning. The cotton plant's dense
foliage also provides shelter and habitat for various small insects and other organisms
[6]
.

1.1.5. Chemical compositions

Table 1.1 is presenting the components and their percentages in cotton fibers.

Table 1.1. Chemical composition of cotton fiber [1]

Component Amount (dry basis)%

Cellulose 94

Protein 1.3

Pectin substance 0.9

Oil, fat & wax 0.6

Ash 1.2

Malic, citric and other organic acids 0.8

Total sugar 0.3

11
 Pigment Trace

Others 0.9

Major chemical composition of cotton fiber are briefly described below:

1.1.5.1. Cellulose

Cellulose, depicted in figure 1.1, is a polymer of ß-D-glucose with a unique

arrangement. The repeating unit of cellulose, cellobiose, comprises two beta glucose
molecules connected at the 1:4 carbon atoms. As each glucose unit rotates 180° around
the molecular axis, it creates a linear polymer chain that is nearly flat, making it ideal
for fiber formation [1].

Figure 1.1. Cellulose structure

1.1.5.2. Protein

These regions originate from the protoplasm of living cells. While fibers do contain a
small amount of nitrogen, not all of it exists as protein. It is suspected that nitrogen-
containing compounds could be linked to the natural pigmentation [1].

1.1.5.3. Pectic substance

Natural cotton inherently contains various derivatives of pectic acid. The primary forms
found are calcium pectate and methyl pectate. However, free pectic acid and methyl
pectate also coexist in the cotton composition [1].

1.1.5.4. Oil, fat and wax

Oils and fats consist of glycerol esters, known as glycerides, combined with higher
saturated and unsaturated fatty acids. Waxes are esters of complex monohydric alcohol
with fatty acid [1]. They are all insoluble in water. Oils and waxes of cotton consists of:

12
  Glycerides which are readily saponifiable oils and fats
 Waxes which are saponifiable with difficulties
 Unsaponifiable oils
 Free fatty acids and
 Traces of soaps

1.2. CARBOXYMETHYL CELLULOSE

1.2.1. Definition

CMC is a derivative of cellulose, containing carboxymethyl groups that are generated

via the reaction of cellulose with chloroacetate in alkali to produce substitutions in the
C2, C3, or C6 positions of glucose units (figure 1.2). Because there are three substituted
positions, the maximum degree of substitution that CMC can have is 3. However,
typically, the degree of substitution of CMC will fluctuate between 0.5 and 1. This is
because the carboxymethylation substitution reaction tends to favor the C6 position
more prominently, primarily due to the absence of significant steric hindrance [7,8].

Figure 1.2. The positions on glucose units where the carboxymethyl group is
substituted

Nevertheless, in practice, Carboxymethyl cellulose is commonly used in its salt form,

specifically the sodium salt, as it dissolves more readily in water and is much more
convenient for preservation.

13
 Figure 1.3. Structure of Sodium Carboxymethyl Cellulose (Na-CMC)

1.2.2. Classification
Có rất nhiều cách để phân loại Na-CMC, như là phân loại theo độ nhớt, phân loại theo
độ tinh khiết và phân loại theo ứng dụng.

1.2.2.1. Classification by viscosity

According to the viscosity (molecular weight), there are 3 types: high viscosity, medium
viscosity and low viscosity (Table 1.2)

Table 1.2. Viscosity of aqueous carboxymethylcellulose sodium 1% w/v solutions.

(Measurements made with a Brookfield LVT viscometer at 25°C.) [5]

Name of Grade Viscosity (mPa)

Low viscosity Akucell AF 0305 10 - 15
Medium viscosity Akucell AF 2785 1500 - 2500
High viscosity Akucell AF 3085 8000 - 12000

Each level of viscosity corresponds to different applications. For instance, low, medium,
and high viscosity Na-CMC are all utilized as suspending agents. However, low
viscosity Na-CMC is typically used in "thin" aqueous solutions. Medium viscosity Na-
CMC is employed to create solutions with a syrup-like appearance. High viscosity Na-
CMC is utilized in mixtures that resemble cream or lotion. Consumers can choose the
appropriate viscosity of Na-CMC based on their specific needs.

1.2.2.2. Classification by purity

Sodium Carboxymethyl Cellulose is categorized into two main types: industrial grade
and food grade. Within the industrial-grade category, it can be further subdivided into
technical-grade and semi-purified Sodium Carboxymethyl Cellulose. Technical-grade
14
Sodium Carboxymethyl Cellulose, also known as crude Na-CMC, generally has a purity
level below 80%. Semi-purified Sodium Carboxymethyl Cellulose falls within the
purity range of 80% to 95%. On the other hand, purified Sodium Carboxymethyl
Cellulose boasts a purity level exceeding 99.5%. It is essential to note that only the
purified form of Sodium Carboxymethyl Cellulose is safe for consumption.

Technical-grade Na-CMC is utilized as a thickener, stabilizer, binder, and dispersant in

industries such as paper manufacturing, textiles, ceramics, and construction. In the paper
industry, technical-grade Na-CMC improves paper strength and water retention. In the
textile industry, it aids in sizing and printing processes. Moreover, it finds applications
in oil drilling fluids and detergents due to its excellent water-solubility and rheological
properties.

Semi-purified Na-CMC s often used as a stabilizer, emulsifier, and thickener in food

products such as sauces, dressings, and ice cream. Additionally, it finds use in
pharmaceutical formulations as a binder and disintegrant in tablet production. In
industrial applications, semi-purified CMC is employed in the manufacturing of
ceramics, detergents, and cosmetics.

Purified Na-CMC is primarily used in the food and pharmaceutical. In the food industry,
it serves as a thickener, stabilizer, and gelling agent in various products, including dairy
products, beverages, and confectionery. In pharmaceuticals, purified CMC is essential
in tablet formulations, as it aids in tablet disintegration and dissolution.

1.2.3. Classification by application

This classification is the most commonly used because it allows for the selection of the
appropriate Na-CMC type for each specific application. Different types of Na-CMC are
categorized based on their intended uses, such as food grade, pharmaceuticals grade,
paper grade, and textiles grade. Although it may appear similar to the purity-based
classification, the application-based classification requires additional criteria to ensure
suitability for specific purposes. For instance, Na-CMC food grade applications must
not only have a purity level of 99.5%, but also meet stringent requirements concerning
heavy metals and microorganisms like E. coli, Coliform, Escherichia coli, and others.

In particular, pharmaceutical-grade Na-CMC must adhere to even more stringent

regulations. To be used in pharmaceutical applications, Na-CMC must meet the

15
standards set forth by pharmacopeias. Table 1.3 shows some examples of pharmacopeial
standards for Na-CMC.

Table 1.3. Pharmacopeial specifications for carboxymethylcellulose sodium [5]

Test JP 2001 PhEur 2005 USP 28

Identification + + +
Characters + + -
pH (1% w/v solution) 6.0 - 8.0 6.0 - 8.0 6.0 - 8.5
Appearance of solution + + -
Viscosity + + +
Loss on drying ≤ 10% ≤ 10% ≤ 10%
Heavy metals ≤ 20𝑝𝑝𝑚 ≤ 20𝑝𝑝𝑚 ≤ 20𝜇𝑔/𝑔
Chloride ≤ 0.64% ≤ 0.25% -
Arsenic ≤ 10𝑝𝑝𝑚
Sulfate ≤ 0.960% - -
Silicate ≤ 0.5% - -
Sodium glycolate - ≤ 0.4% -
Starch + - -
Sulfated ash - 22.0 – 33.3% -
Organic volatile
- - +
impurities
Assay (of sodium) 6.5 - 8.5% 6.5 – 10.8% 6.5 – 9.5%
1.2.4. Typycal properties
The properties of Na-CMC depend on two main factors: the degree of substitution (DS)
and purity. The degree of substitution of pharmaceutical-grade Na-CMC will range from
[5]
0.9 to 1.2 , and the purity must be greater than 99.5%. The characteristics of
pharmaceutical-grade CMC will include:

 Density (bulk): 0.52 g/cm3

 Density (tapped): 0.78 g/cm3
 Dissociation constant: pKa = 4.30
 Melting point: browns at approximately 227°C, and chars at approximately 252°C

16
 Moisture content: typically contains less than 10% water. However,
carboxymethylcellulose sodium is hygroscopic and absorbs significant amounts of
water at temperatures up to 37°C at relative humidities of about 80%
 Solubility: practically insoluble in acetone, ethanol (95%), ether, and toluene.
Easily dispersed in water at all temperatures, forming clear, colloidal solutions.
The aqueous solubility varies with the degree of substitution (DS)
 Viscosity: various grades of carboxymethylcellulose sodium are commercially
available that have differing aqueous viscosities; see Table 1.2. Aqueous 1% w/v
solutions with viscosities of 5–13 000 mPa s (5–13 000 cP) may be obtained. An
increase in concentration results in an increase in aqueous solution viscosity.
Prolonged heating at high temperatures will depolymerize the gum and
permanently decrease the viscosity. The viscosity of sodium
carboxymethylcellulose solutions is fairly stable over a pH range of 4–10. The
optimum pH range is neutral.

1.2.5. Stability and Storage Conditions [5]

Carboxymethylcellulose sodium is a stable material, but it is hygroscopic, meaning it
can absorb a significant amount of water (>50%) under high-humidity conditions. In
tablet formulations, this water absorption has been linked to a decrease in tablet hardness
and an increase in disintegration time.

When dissolved in water, the aqueous solutions of carboxymethylcellulose sodium

remain stable within a pH range of 2 to 10. However, precipitation can occur at pH levels
below 2, and the viscosity of the solution decreases rapidly above pH 10. The optimal
pH range for maximum viscosity and stability of solutions is typically between pH 7 to
9.

To sterilize carboxymethylcellulose sodium, it can be heated in its dry state at a

temperature of 160°C for 1 hour. However, this process leads to a significant decrease
in viscosity and some deterioration in the properties of solutions prepared from the
sterilized material.

Alternatively, aqueous solutions of carboxymethylcellulose sodium can also be

sterilized by heating, but this method also results in some reduction in viscosity.
Autoclaving the solutions leads to a viscosity reduction of about 25%, but this decrease

17
is less pronounced than in solutions prepared from material sterilized in its dry state.
The extent of viscosity reduction depends on the molecular weight and degree of
substitution; higher molecular weight grades generally undergo a greater percentage
reduction in viscosity. Additionally, sterilizing solutions through gamma irradiation also
leads to a reduction in viscosity.

Aqueous solutions stored for prolonged periods should contain an antimicrobial

preservative.

The bulk material should be stored in a well-closed container in a cool, dry place.

1.2.6. Incompatibilities
Carboxymethylcellulose sodium is incompatible with strongly acidic solutions and with
the soluble salts of iron and some other metals, such as aluminum, mercury, and zinc.
Precipitation may occur at pH < 2, and also when it is mixed with ethanol (95%).

Carboxymethylcellulose sodium forms complex coacervates with gelatin and pectin. It

also forms a complex with collagen and is capable of precipitating certain positively
charged proteins.

1.2.7. Safety
Carboxymethylcellulose sodium is utilized in various forms, including oral, topical, and
certain injectable formulations. It finds extensive application in cosmetics, toiletries, and
food products and is generally considered safe and non-irritating. Nonetheless, when
consumed orally in large quantities, it can act as a laxative. For therapeutic purposes,
medium- and high-viscosity grades of carboxymethylcellulose sodium, totaling 4–10 g
per day in divided doses, have been employed as bulk laxatives.

Regarding its use as a food additive, the World Health Organization (WHO) has not
specified a daily intake limit since the levels needed to achieve the intended effects were
not deemed harmful to health. However, animal studies have shown that subcutaneous
administration of carboxymethylcellulose sodium can cause inflammation, and in some
cases, repeated injections have been associated with fibrosarcomas at the injection site.

Furthermore, hypersensitivity and anaphylactic reactions have been observed in cattle

and horses, linked to the presence of carboxymethylcellulose sodium in parenteral
formulations like vaccines and penicillins..

18
LD50 (guinea pig, oral): 16 g/kg

LD50 (rat, oral): 27 g/kg

1.2.8. Synthesis of Sodium carboxymethyl cellulose pharmaceutical grade

Initially, we observe that for pharmaceutical grade, two primary conditions must be
fulfilled. The first requirement pertains to the DS falling within the range of 0.9 to 1.2,
while the second condition demands a purity level exceeding 99.5%. The fulfillment of
the first criterion is connected to the fusion reaction, while the adherence to the second
criterion is associated with the purification process.

1.2.8.1. Synthesis reaction of Sodium carboxymethyl cellulose

Synthesis process of Na-CMC included of two main reactions: Alkalization and

Etherification.

a. Alkalization reactions

NaOH solution-induced swelling of cellulose is recognized as alkalization reaction.

Figure 1.4. Alkalization of Cellulose in NaOH solution

Alkalizing cellulose with NaOH is a vital part of CMC synthesis because it is required
to generate alkali cellulose, an important intermediate in the subsequent reaction
process. This step disrupts the crystalline structure of cellulose, resulting in the
formation of a more amorphous structure, which is more reactive towards subsequent
chemical modification [7].

It is typical to control the temperature at 35°C for 1 hour while alkalizing cellulose using
[8]
NaOH . In addition, the concentration of NaOH plays a significant role in the
alkalization reaction and consequently affects the degree of CMC produced. Higher
NaOH concentrations can result in increased degrees of substitution, improved

19
 [9]
solubility, and viscosity of the CMC product . Hence, it is crucial to select the
appropriate NaOH concentration.

b. Etherification reaction

After alkalization, alkali cellulose (Na-Cellulose) undergoes a reaction with Sodium

Monochloroacetic acid (Na-MCA) that introduces carboxymethyl groups onto the
cellulose backbone.

Figure 1.5. Etherification of alkali cellulose to obtain Sodium carboxymethyl cellulose

The etherification reaction is carried out at a temperature range of 60-65°C [10,11]. In

theory, the molar ratio of Na-MCA to anhydroglucose unit (AGU) in the
carboxymethylation reaction is typically between 1 to 3, and an increase in this ratio
should correspond to an increase in the degree of substitution. However, multiple studies
have shown that while the degree of substitution does initially increase with an increase
in the Na-MCA/AGU ratio, it eventually reaches a maximum and then begins to
decrease at higher ratios [10,12]. One explanation for this phenomenon is that a higher
concentration of Na-MCA may lead to increased side reactions between Na-MCA and
NaOH, thereby reducing the yield of the substitution reaction [10]. Therefore, it is
important to carefully consider the Na-MCA/AGU ratio along with the NaOH/Na-MCA
ratio to maximize the yield and minimize side effects.

Figure 1.6. Side reaction between Na-MCA and NaOH to create Sodium Glycolate

20
1.2.8.2. Purification process of Sodium carboxymethyl cellulose

Upon analyzing the reaction equations and referring to the pharmacopoeial standards
(as shown in Table 1.3), it becomes evident that the most crucial impurities requiring
purification in the product are sodium chloride (NaCl) and sodium glycolate (HNa).
Both of these impurities are water-soluble sodium salts, making them easily removable
through water-based washing methods. However, the main product, Na-CMC, is also
soluble and can be readily absorbed. Nevertheless, Na-CMC exhibits insolubility in
ethanol. Hence, a solvent system comprising water and ethanol would be suitable for
washing away the impurities while ensuring product yield and quality. Nonetheless,
further investigation is required to determine the optimal usage of this solvent system.

21
 CHAPTER 2

MATERIALS AND RESEARCH METHODS

2.1. MATERIALS

The raw materials for synthesizing Na-CMC include Cotton, Sodium hydroxide
(NaOH), Isopropanol (IPA), Monochloroacetic acid (MCA), and Acetic acid
(CH3COOH), Ethanol (EtOH).

2.1.1. Cotton
In this study, the cotton used consists of short cotton fibers obtained from the fiber
production facility of HOTHA Vietnam Company in Buon Don, Dak Lak. These short
cotton fibers have small fiber sizes, measuring only 1 to 2mm. A previous study [12] has
shown that as the cellulose fiber size decreases, it results in higher degree of substitution
(DS) of CMC.
[6]
2.1.1.1. Physiccal properties

Cotton, a natural cellulose fiber, exhibits a diverse range of physical properties. The
color of cotton fibers can vary, including options such as white, creamy white, bluish-
white, yellowish white, or grey. In terms of strength, cotton is moderately strong, with a
tenacity of 3-5 gm/den. Interestingly, its wet strength, at 20%, exceeds its dry strength,
making moisture a significant factor influencing its strength. Cotton has low elongation
at break, typically ranging from 5% to 10%, and is considered inelastic and rigid,
although it does show some elastic recovery. At a 2% extension, it achieves 74%
recovery, and at 5%, it reaches 45% recovery.

The specific gravity of cotton fiber is approximately 1.54. Regarding its response to
heat, cotton demonstrates excellent resistance to degradation, yet at temperatures around
120°C, it may begin to turn yellow. Decomposition becomes evident at temperatures
above 150°C, and exposure to 240°C for a few minutes can severely damage the cotton
fiber, which also readily burns in the presence of air.

When exposed to sunlight, cotton fibers gradually lose strength and take on a yellowish
hue. Furthermore, heat-induced oxidation contributes to the degradation of cotton.
Notably, ultraviolet (UV) light and visible light can also cause damage to the fibers.

22
In terms of aging, carefully stored cotton experiences minimal loss of strength over time.
Even after 50 years of storage, the difference between aged cotton and new fibers
remains slight. Understanding these comprehensive physical properties is crucial for the
practical applications of cotton in various industries, particularly in textile
manufacturing and other fields where its unique characteristics are valued. Researchers
and scientists continuously study and analyze these properties to improve cotton-based
materials and optimize their performance.

2.1.1.2. Chemical properties

a. Cotton in alkalis

When immersed in an alkali solution, such as sodium hydroxide (NaOH) or potassium

hydroxide (KOH), several chemical reactions and changes occur in the cotton fibers.

 Swelling: Cotton fibers undergo significant swelling in an alkali solution. Alkalis

break the intermolecular hydrogen bonds between cellulose chains, leading to the
separation of these chains and an increase in the space between them. As a result,
the cotton fibers swell, making them more pliable and easier to work with during
various processes.
 Alkali Cellulose Formation: In an alkali solution, cellulose reacts with the alkali
to form alkali cellulose (Fugure 1.4)
b. Cotton in acidic

When cotton comes into contact with an acidic solution, such as hydrochloric acid (HCl)
or sulfuric acid (H2SO4), various chemical reactions and changes occur in the cotton
fibers. The behavior of cotton in an acidic solution is notably different from its behavior
in an alkali solution due to the nature of the chemical reactions involved.

 Acid Hydrolysis: Cotton fibers, which are primarily composed of cellulose,

undergo acid hydrolysis in acidic solutions. Acid hydrolysis breaks down the
cellulose chains into smaller sugar units called glucose. This process involves the
cleavage of the glycosidic bonds between the glucose units in cellulose, leading to
the degradation of the cotton fibers.
 Reduced Swelling: Unlike in alkali solutions, cotton fibers do not swell
significantly in acidic solutions. Instead, the acid hydrolysis causes a reduction in
the size and dimensions of the fibers.

23
2.1.2. Sodium hydroxide (NaOH)
2.1.2.1. Physical properties
 State: Solid
 Colour: Colorless or white
 Melting point: 323℃
 Density: 2.13 g/cm3
 Molecular mass: 39.997 g/mol
 Solubility:
 In water: 418 g/L (0℃), 1000 g/L (25℃), 3370 g/L (100℃).
 In methanol: 238 g/L
 Insoluble in ether
2.1.2.2. Chemical properties
 It has an ionic bond between the Na(+1) ion and OH(-1) ion.
 It can react with protic acids to form water and salts.
 It has high acidity of 13.
 Sodium hydroxide is a popular base that is used for leaching amphoteric
hydroxides or oxides.
 There is a covalent bond, between oxygen and hydrogen in the hydroxide.

2.1.3. Isopropanol (IPA)

2.1.3.1. Physical properties
 State: Liquid
 Colour: Colorless
 Boiling point: 82.6℃
 Density: 0.786 g/cm3
 Molecular mass: 60.1 g/mol
 Concentration in azeotrope point: 87.4 – 87.7%
 Isopropyl alcohol is an organic polar molecule, miscible in water, ethanol and
chlroroform.
2.1.3.2. Chemical properties

24
Isopropyl alcohol can be oxidized to acetone (equivalent ketone). This can be achieved
with oxidizing agents such as chromic acid, or with isopropyl alcohol dehydrogenation
over a heated copper catalyst.

(CH3)2CHOH → (CH3)2CO + H2

In reduction of Meerwein-Ponndorf-Verley and other transfer hydrogenation reactions,

isopropyl alcohol is often used as both solvent and hydride source. Isopropyl alcohol
can be converted to 2-bromopropane using tribromide phosphorus, or dehydrated to
propene by sulfuric acid heating.

Like most alcohols, isopropyl alcohol reacts to the formation of alkoxides that can be
called isopropoxides with active metals such as potassium. The aluminum reaction
(initiated by a mercury tracer ) is used to prepare the aluminum isopropoxide catalyt

2.1.4. Monochloroacetic acid (MCA)

2.1.4.1. Physical properties
 State: Solid
 Colour: Colorless or white
 Melting point: 63℃
 Density: 1.58 g/cm3
 Molecular mass: 94.5 g/mol
 Soluble in water, methanol, acetone, diethyl ether, benzene, chloroform, ethanol
and IPA
 Solubility in water: 85.8 g/100 mL (25°C)
 Acidity (pKa): 2.86
2.1.4.2. Chemical properties

The chemical properties of chloroacetic acid are varied and are shown below.

The carboxylic group of chloroacetic acid is highly reactive due to the presence of alpha
chlorine.It reacts with inorganic bases, oxides, carbonates, and organic bases resulting
in the formation of salts. The salts may also form adducts with chloroacetic acid.

ClCH2COOH + NaOH → ClCH2COONa + H2O

In reaction with alcohols or olefins, chloroacetic acid undergoes an esterification

reaction.

25
 ClCH2COOH + NaOH → ClCH2COONa + H2O

Chloroacetic acid reacts with POCl3, PCl3, PCl5,SOCl2 and COCl2 (phosgene) resulting
in the formation of chloroacetyl chloride.

ClCH2COOH + PCl5/PCl3/SOCl2 → ClCH2COCl

The chlorine atom in chloroacetic acid can undergo nucleophilic substitution, forming
an essential intermediate in many synthesis reactions.

ClCH2COOH + aq. NaOH → HOCH2COOH + NaCl

2.1.5. Acid acetic (CH3COOH)

2.1.5.1. Physical properties
 State: Liquid
 Colour: Colorless
 Boiling point: 118℃
 Density: 1.05 g/cm3
 Molecular mass: 60.052 g/mol
 Acetic acid is infinitely miscible in water, also miscible with alcohol, glycerol, ether,
carbon tetrachloride.
 Acetic acdi insoluble in carbon disulfide
2.1.5.2. Chemical properties
 Acetic acid loses one hydrogen molecule due to the carboxyl functional group.
This causes a big ionization of the compound, as shown by the reaction:
CH₃COOH ⇌ CH₃COO⁻ + H⁺
 Acetic acid’s acidic character results from the proton discharge mentioned by the
equilibrium process above.
 Acetic acid’s conjugate base is acetate (CH₃COO⁻).
 As may be observed from the pH of an ethanoic acid solution at 1.0M
concentration, acetic acid does not entirely dissociate.
 Acetic acid is a polar, protic solvent with a liquid dielectric constant of 6.2.

2.1.6. Ethanol (EtOH)

2.1.6.1. Physical properties
 State: Liquid

26
 Colour: Colorless
 Boiling point: 78.37℃
 Density: 0.789 g/cm3
 Molecular mass: 46.08 g/mol
 Concentration in azeotrope point: 95.635%
 Ethanol is a versatile solvent, miscible with water and with many organic solvents,
including acetic acid, acetone, benzene, carbon tetrachloride, chloroform, diethyl
ether, ethylene glycol, glycerol, nitromethane, pyridine, and toluene
2.1.6.2. Chemical properties
a. Dehydration

There is a loss of water molecules when ethanol reacts with concentrated sulphuric acid
at 443K, i.e. dehydrated to form ethene.

b. Reaction with sodium:

The reaction of sodium metal with ethanol produces sodium ethoxide and hydrogen
gas.

c. Oxidation

Ethanoic acid is formed when ethanol is oxidised with alkaline potassium permanganate
(KMnO4) or acidified potassium dichromate (K2Cr2O7)

The colour change occurs during this reaction where the orange colour of K 2Cr2O7 turns
to green. This reaction can be used for the identification or confirmation of the alcohol
group.

d. Esterification:

Alcohol in reaction with a carboxylic acid produces a compound having a fruity odour.
This compound is referred to as an ester. This reaction is known as esterification.

Ethanol on reaction with ethanoic acid in the presence of concentrated sulphuric acid
forms ethyl ethanoate (an ester compound).

e. Dehydrogenation:

27
The process of dehydrogenation occurs when vapours of ethanol pass over hot copper
(Cu) at 573K. In this reaction, copper is used as a catalyst. Dehydrogenation of ethanol
forms acetaldehyde (CH3CHO).

f. Combution

Ethanol is a volatile and highly inflammable liquid. Carbon dioxide and water are
formed when ethanol reacts with oxygen.

2.2. RESEACH METHODS

The main aim of this study was to produce Sodium Carboxymethylcellulose (Na-CMC)
with a degree of 0.9-1 and with %NaCl ≤ 0.25% and %HNa ≤ 0.4% (PhEur 2005
pharmacopeia, table 1.3).

2.2.1. Methodology for studying the technological conditions of the reaction to

produce Na-CMC.

Experimental research methods to investigate the factors affecting the reaction process
include:

 NaOH solution concentration (w/v)

 Molar ratio MCA/AGU (mol/mol)
 Molar ratio NaOH/MCA (mol/mol)

These factors will be investigated on a number of fixed reaction conditions as follows:

 Solvent: Isopropanol 99.97%

 IPA/cotton cellulose = 20 (mL/g)
 Alkylation reaction temperature: 35℃
 Alkylation reaction time: 60 minutes
 Etherification reaction temperature: 65℃
 Etherification reaction time: 90 minutes

These investigations were conducted on the various stages of the reaction: Three grams
of cotton cellulose was added to 60mL of isopropanol under continuous stirring for 30
minutes. Then, NaOH solution was dripped into the mixture and further stirred for 1
hour at 35°C. After 1 hour, MCA solution (MCA dissolved in IPA) was added to the
reaction flask and continued stirring for 30 minutes. Subsequently, the temperature was

28
elevated to a range of 60-65°C, and the carboxymethylation reaction occurred for a
duration of 90 minutes. After the reaction, the mixture was neutralized with acetic acid
and underwent multiple washes with EtOH to eliminate any impurities present. The
resulting product was dried at 60°C until a constant weight was achieved, and then stored
in a polyethylene bag at room temperature.

2.2.1.1. NaOH solution concentration (w/v)

This investigation focuses on the efficiency of cellulose alkylation with different

concentrations of NaOH. The objective was to determine the optimal concentration of
NaOH to achieve the highest substituent (DS), i.e. the greatest potential for
carboxymethyl substitution to the cellulose chain. The substitution of carboxymethyl
into the cellulose chain through alkylation is an important chemical process in the
conversion of cellulose into products with novel properties. However, choosing the right
NaOH concentration is extremely important, because not every higher NaOH
concentration will increase the reaction efficiency.

Therefore, investigating the concentration of NaOH from dilute to concentrated in this

study helps to determine the optimal concentration level to achieve the highest efficiency
without unduly damaging the cellulose structure. The concentration of NaOH was
specifically investigated with concentrations of 10%, 20%, 25%, 30%, 40%, 50% and
60% w/v.

After finishing the reaction, the product will be analyzed for substituent (DS).
Substituent degree is an index used to indicate the number of functional groups present
in the cellulose structure after substituting, and it will indicate the degree of
carboxymethyl substitution to the cellulose chain. DS analysis for each concentration of
NaOH will help to determine the relationship between NaOH concentration and
carboxymethyl substitution efficiency.

Based on the results of DS analysis, the study will be able to show which NaOH
concentration is the most optimal to achieve the highest cellulose alkalization efficiency
and enhance the ability to substitute carboxymethyl into the cellulose chain.

2.2.1.2. Molar ratio MCA/AGU (mol/mol)

The molar ratio of MCA/AGU plays a crucial role in determining the degree of
substitution (DS) in the synthesis of sodium carboxymethyl cellulose (Na-CMC).

29
Theoretically, a higher MCA/AGU ratio is essential to enhance the efficiency of the
etherification reaction, as MCA serves as the primary carboxymethyl substituent for the
cellulose structure. By increasing the MCA/AGU ratio, more MCAs participate in the
reaction, leading to an elevated DS of the product, indicating a higher capacity for
carboxymethyl substitution in the cellulose chain.

However, practical studies have revealed that continuous increases in the MCA/AGU
[10,12]
ratio do not always result in a persistent rise in DS . Instead, the DS initially
increases but eventually reaches a point where it starts to decline again. Several factors
contribute to this phenomenon, which will be discussed later. Moreover, the main goal
of this study was to identify the optimal molar ratio of MCA/AGU that would yield a
product with a DS ranging from 0.9 to 1. Going beyond this optimal range by
excessively increasing the MCA/AGU ratio would be inefficient and wasteful.

To prevent the excessive consumption of MCA for potential side reactions, I initiated
the investigation of the MCA/AGU ratio starting from 1 and incrementally increased it
until achieving the desired DS range. By doing so, I aim to find the precise ratio that
provides the highest efficiency and quality in producing carboxymethyl cellulose while
staying within the desired DS range.

2.2.1.3. Molar ratio NaOH/MCA (mol/mol)

In the synthesis of sodium carboxymethyl cellulose (Na-CMC), both NaOH (excess
after alkalization) and Na-MCA are present. These two compounds can react with each
other, yielding a byproduct called Sodium glycolate (HNa). The occurrence of this side
reaction is closely related to the molar ratio of NaOH and MCA. Therefore, it is
necessary to investigate an appropriate NaOH/MCA ratio to minimize the formation of
byproducts and reduce the wastage of reactants. Additionally, we observe that a
sufficient amount of NaOH is needed to alkylate at least one -OH group on the cellulose
chain, converting MCA to Na-MCA. Thus, we will commence the investigation of the
NaOH/MCA molar ratio from 2.5, which appears to be reasonable. After conducting this
study, we will analyze the DS (degree of substitution) of the product to understand the
correlation between this ratio and the quality of Na-CMC obtained after the reaction.

30
2.2.2. Methodology for studying the purification process of Na-CMC.
As presented in the introduction, the purification of Na-CMC involves washing it with
a suitable washing solvent. The two main substances of concern after Na-CMC
purification are NaCl and HNa. As both are sodium salts, they are highly soluble and
can be easily washed away by water. However, Na-CMC itself is a water-soluble and
water-absorbing substance. Therefore, using water alone for washing would
compromise the product. Additionally, considering the characteristics of Na-CMC, it is
not soluble in EtOH (ethanol). Thus, it would be reasonable to use an EtOH-H2O solvent
system for washing the product.

It is essential to note that apart from the efficiency of the washing solvent, the number
of washing cycles and the volume of solvent used per washing also significantly impact
the refining process's effectiveness.

Therefore, the refinement process of Na-CMC will be investigated based on three

factors:

 The ratio of EtOH-H2O solvent: starting from a ratio of 70% v/v EtOH and
gradually increasing.
 The number of washing cycles.
 The volume of solvent used per washing cycle.

After each refinement study, the refined product will be analyzed for the presence of
NaOH and HNa residues. The investigation will continue until the NaOH residue is
below 0.25% and the HNa residue is below 0.4%.

2.2.3. Analysis method

2.2.3.1. Determine degree of substitution [13]
a. Principle

First, Na-CMC is converted to CMC-acid by reacting with HNO3

31
 Figure 2.1. Reaction between Na-CMC and HNO3

Afterwards, CMC-acid will undergo a reaction with an excess amount of NaOH,

converting back to Na-CMC. The surplus NaOH will then be titrated using hydrochloric
acid (HCl) in the presence of phenolphthalein as an indicator.

b. Procedure

Weigh approximately 1 g of the sample in to a 100mL round bottom flask and add 20mL
of ethano 96%. Stir the mixture with an magnetic stirrer until a good slurry is obtained.
Add 1.5 mL of HNO3, while agitating, and continue agitation for 1 to 2 minutes. Heat
the slurry and boil for 5 minutes. Remove the heat and continue agitation for 15 minutes.
Decant the supernatant liquid through the filter and transfer the precipitate to the filter
with ethanol 96%. Wash the precipitate with ethanol 80% that has been heated to 60°C,
until all of the acid has been removed. Then, dry the dish and contents, uncovered for 3
hours at 105°C. Weigh, to the nearest 0.01 g the dried acid carboxymethylcellulose into
a 250 mL round bottom flask. Add 100 mL of water and 250 mL of 0.5 N NaOH solution,
while stirring. Heat the solution to boiling, and boil for 15 to 30 minutes. Titrate the
excess NaOH, while the solution is hot, with the 0.5 N HCl to phenolphthalein end point.

Degree of substituent is calculated as follows:

𝐁𝐂 𝐃𝐄
𝐀= (1)
𝐅

𝟎.𝟏𝟔𝟐𝐀
𝐆= (2)
𝟏 𝟎.𝟎𝟓𝟖𝟒𝐀

Where:

A = milliequivalents of acid consumed per gram of sample,

B = NaOH solution added, mL,

C = normality of the HCl,

F = acid carboxymethylcellulose used, g,

162 = gram molecular mass of the anhydroglucose unit of cellulose, and

58 = net increase in molecular mass of anhydroglucose unit for each carboxymethyl

group substituted.

32
2.2.3.2. Determine residues of sodium chloride (NaCl) [13]
a. Principle

NaCl residue determined by Mohr's method. Silver nitrate (AgNO 3) solution is used as
the titrant, and a potassium chromate (K2CrO4) indicator is added to the analyte solution.
When all chloride ions have reacted with silver ions (Ag+) to form a silver chloride
(AgCl) precipitate, any excess silver ions will react with the potassium chromate
indicator, forming a red-colored silver chromate precipitate. The appearance of the red
color signals the endpoint of the titration, allowing the concentration of chloride ions to
be calculated.

b. Procedure

In this study, we used Mohr's method to determine the NaCl residue in CMC: weigh 1 g
of the sample, to the nearest 0.0001 g, into a 100 mL beaker. Add 23 mL of water and 2
mL of H2O2 (30%). Place the beaker on a steam bath, stirring occasionally to achieve a
nonviscous solution. Add 2 to 3 drops of 5% K2CrO4 solution to the cooled solution and
shake until the solution is even. Prepare 0.01N AgNO3 solution and standardize it with
the standard 0.01 N NaCl solution. Load the burette with the standardized AgNO 3
solution and titrate until the appearance of the brick-red color of Ag2Cr2O4. Repeat the
process two more times and calculate the average value.

Residures percent of NaCl is calculated as follows:

%𝐍𝐚𝐂𝐥 = 𝐇 × 𝐄 × 𝟓𝟖. 𝟒𝟒 (3)

where:

H = normality of the standardized AgNO3,

E = AgNO3 solution consumed, mL,

58.44 gram molecular mass of sodium chloride NaCl.

2.2.3.3. Determine residues of sodium glycolate (HNa) [13]
a. Principle

UV-VIS method is an analytical method based on the absorption effect that occurs when
matter molecules interact with electromagnetic radiation. When a light beam of suitable
wavelength passes through a dye solution, the absorbing molecules will absorb part of

33
the beam energy and part of the light transmitted through the solution. Determine the
intensity of the transmitted light beam by which the concentration of the solution can be
determined. The absorption of light by the solution obeys the Bughe – Lambert – Beer
law:

A= 𝜺×𝑪×𝑰

Where:

𝜀 – Molecular absorption coefficient

C – Concentration of solution (mol/L)

I – Light transmission thickness (cm)

Glycolic acid is known to give a reddish color when heated with 2,7-
dihydroxynaphthalene in concentrated sulfuric acid and this reaction has been utilized
for qualitative detection of glycolic acid.

b. Preparation of Calibration Curve

Into a series of five 100-mL volumetric flasks accurately introduce 1, 2, 3, and 4-mL
aliquots of the standard glycolic acid solution, reserving the fifth flask for a blank. Add
sufficient water to each flask to give a total volume of 5 mL. Add 5 mL of glacial acetic
acid, make up to volume with acetone and mix. These solutions will contain 0, 1, 2, 3
and 4 mg of glycolic acid, respectively.

Pipet 2 mL of each of these solutions into individual 25-mL volumetric flasks. Place the
uncovered flasks upright in a boiling water bath for exactly 20 min to remove the
acetone. Remove the flasks from the bath and cool.

To each flask add 20 mL of 2,7-dihydroxy naphthalene reagent as follows: Add 5 mL of

reagent initially, mix thoroughly, then add the remaining 15 mL of reagent and mix.
Cover the mouth of the flasks with a small piece of aluminum foil and place upright in
the boiling water bath for 20 min. Remove from the bath, cool, and make up to volume
with H2SO4.

Measure the absorbance of each solution at 540 nm against the blank solution. Plot the
milligrams of glycolic acid in the original 100 mL of solution against absorbance to
give a calibration curve.

34
A calibration curve was estabished by correlating the absorbance values with glycolic
acid concentration, as demonstrated in Figure 2.2.

1.2

Absorbance at 540 nm
0.8

0.6
y = 242.52x + 0.0234
0.4 R² = 0.9936

0.2

0
0 0.0005 0.001 0.0015 0.002 0.0025 0.003 0.0035 0.004 0.0045
Glycolic acid (g)

Figure 2.2. A calibration curve for colorimetric determination of glycolic acid with the
2,7-dihydroxynaphthalene reagent

c. Procedure

Weigh about 0.5 g of the sample and dissolve it completely by 5 mL of acetic acid
followed by 5 mL of water. Precipitate all of carboxymethyl cellulose with 50 mL of
acetone and 1 g of NaCl. Filter through filter paper to remove precipitate, the filtrate is
collected in a 100 mL volumetric flask, and the filter residue is washed with
approximately 30 mL of acetone. Make up to volume with acetone and mix. In another
100 mL volumetric flask, blank solution is prepared by add 5 mL of acetic acid, 5 mL
of water and make up with acetone. Pipette 2 mL of the solution from the specimen and
2 mL of the blank solution into separate 25-mL volumetric flasks, add 20 mL of 2,7-
dihydroxy naphthalene reagent and heat in a water bath for 20 min. Make up to volume
with H2SO4.

Measure the absorbance of solution at 540 nm against the blank solution by a

spectrophotometer. Using the observed absorbance, refer to the calibration curve and
read the corresponding milligrams of glycolic acid.

2.2.3.4. Determine residues of sodium acetate (CH3COONa) [14]

a. Principle

35
The method employ perchloric acid titration method, dissolve the sample in glacial
acetic acid and titrate with perchloric acid – acetic acid standard solution. Endpoint is
detected by potentiometric titration with glass / reference electrodes.

CH₃COONa ＋ HClO₄ → CH₃COOH ＋ NaClO₄

b. Procedure

The reagents in this method include:

 Titrant: 0.1 mol/L perchloric acid in glacial acetic acid standard solution
 Titration solvent: Glacial acetic acid
 Electrolyte: Saturated sodium perchlorate in glacial acetic acid (For inner solution
of reference electrode)

Measurement procedure:

(1) Take 0.2 g of the sample into a 100 mL tall-beaker and accurately weigh it.

(2) Add 50 mL of acetic acid and dissolve the sample.

(3) Immerse the electrodes and start titration with 0.1 mol/L perchloric acid in glacial
acetic acid standard solution. Perform blank test without sample.

2.2.3.5. Determine the moisture

Weigh 3 to 5 g of the sample to the nearest 0.001 g in a tared and covered weighing
bottle. Place the bottle in an oven at 105°C for 2 h with the cover removed. Cool the
bottle in a desiccator, replace the cover, and weigh. Replace the sample in the oven for
30 min, cool, and reweigh. Continue this procedure to a mass loss of not more than 5
mg for 30 min drying time.

Moisture of product is calculated as follows:

M = (A/B) x 100 (4)

Where:

A – Mass loss on heating, g

B – Sample used,

36
 CHAPTER 3

RESULTS AND DISCUSSIONS

3.1. RESULTS OF THE EXPERIMENT TO DETERMINE THE REACTION
TECHNOLOGY CONDITIONS FOR NA-CMC PRODUCTION
3.1.1. Investigate the effect of NaOH concentration

The basis of the investigation: Change of NaOH concentration at the values of 10%,
20%, 25%, 30%, 40%, 50%, 60% (w/v) while keeping the ratio MCA/AGU=1.3
(mol/mol) and the ratio NaOH/MCA=3 (mol/mol).

Chemicals were quantified according to Table 3.1.

Table 3.1. Study of the Influence of NaOH Concentration

NaOH
Sample Cotton (g) IPA (mL) MCA (g)
m (g) 𝑽𝑯𝟐 𝑶 (mL) w/v%
NC1 3 60 3 30 10 2.27
NC2 3 60 3 15 20 2.27
NC3 3 60 3 12 25 2.27
NC4 3 60 3 10 30 2.27
NC5 3 60 3 7.5 40 2.27
NC6 3 60 3 6 50 2.27
NC7 3 60 3 5 60 2.27

The experimental samples were analyzed and the results obtained are shown in Table
3.2 and Figure 3.1.

Table 3.2. Sample analysis results in investigating the effect of NaOH concentration

Sample NaOH w/v% DS

NC1 10 -
NC2 20 0.547
NC3 25 0.582
NC4 30 0.645
NC5 40 0.82

37
 NC6 50 0.92
NC7 60 1.14

1.2 1.14

Degree of Substitution (D.S)

1 0.92
0.81
0.8
0.645
0.582
0.6 0.547

0.4

0.2

0
15 20 25 30 35 40 45 50 55 60 65
NaOH concentration (% w/v)

Figure 3.1. The change of DS with different concentrations of NaOH

Upon examining the data table, it is evident that the DS values increase as the NaOH
concentration increases from 20% to 60%, which is in accordance with prior researches
published [9,10,15]. This can be attributed to the increase in the concentration of hydroxide
ions (OH-) in the reaction mixture. These OH- ions serve to break the glycosidic bonds
between the glucose units in the cellulose molecule, making it more susceptible to the
carboxymethylation reaction. There is no DS value for sample NC1 (i.e., NaOH 10%
w/v) because at such a low concentration, almost no alkaline cellulose is produced,
resulting in extremely low carboxymethyl substitution efficiency. The product of this
sample cannot even dissolve completely in water, making it impossible to determine its
DS (Figure 3.2).

Please note that the investigation in the study was limited to a maximum NaOH
concentration of 60% (w/v) due to the difficulty of preparing NaOH solutions with
higher concentrations, primarily because of the limited solubility of NaOH in water.
Although the 60% NaOH concentration yielded promising results surpassing our
expectations (initial target 0.9 < DS < 1), we determined that the optimal concentration
for further experiments would be 50%. This decision was based on observations made
during the testing of the physical properties of the Na-CMC samples when dissolved in

38
water. We found that the Na-CMC sample produced using the 60% NaOH solution
exhibited higher potential but had significant drawbacks. It took a considerable amount
of time to dissolve, and the resulting solution under the lamp still contained small
cellulose fibers (Figure 3.3). These findings indicate that while the reaction with NaOH
showed high potential, the quality of Na-CMC produced was unsatisfactory. Similar
observations were reported in previous research [15]. This phenomenon can be attributed
to the sample's high heterogeneity, which leads to a non-statistical distribution of
carboxymethyl groups substituting the anhydroglucose units.

Thus, the concentration of NaOH 50 %w/v will be selected for further investigation.

Figure 3.2. Sample product image NC1, almost no reaction occurs so the product
looks like the original cotton.

39
 Figure 3.3. Results when dissolving sample NC7 in water

3.1.2. Investigate the effect of molar ratio MCA/AGU

The basis of the investigation: Change of molar ratio MCA/AGU at the values of 1, 1.1,
1.3, 1.5 while keeping the NaOH concentration is 50 w/v% and the ratio NaOH/MCA=3
(mol/mol).

Chemicals were quantified according to Table 3.3.

Table 3.3. Study of the Influence of MCA/AGU ratio (mol/mol)

NaOH
Sample Cotton (g) IPA (mL) MCA (g)
m (g) 𝑽𝑯𝟐 𝑶 (mL) w/v%
MA1 3 60 3 6 50 1.75
MA2 3 60 3 6 50 1.92
MA3 3 60 3 6 50 2.27
MA4 3 60 3 6 50 2.62

The experimental samples were analyzed and the results obtained are shown in Table
3.4 and Figure 3.2.

Table 3.4. Sample analysis results in investigating the effect of MCA/AGU ratio
(mol/mol)

Sample MCA/AGU (mol/mol) DS

MA1 1 0.584
MA2 1.1 0.813
MA3 1.3 0.95
MA4 1.5 1.041

As the amount of MCA used in the reaction increases, it is apparent that the DS of Na-
CMC also increases. The findings of research [9] yield a comparable result. This can be
attributed to the fact that an increase in MCA quantity results in more carboxymethyl
groups being introduced onto the cellulose, thereby raising the degree of substitution in
the resulting Na-CMC product

40
 1.2

1
1.041

Degree of substitution (DS)

0.95
0.8
0.813

0.6
0.584
0.4

0.2

0
0.8 0.9 1 1.1 1.2 1.3 1.4 1.5 1.6
MCA/AGU (mol/mol)

Figure 3.4. The change of DS with different mole ratio MCA/AGU

However, while the highest degree of CMC was obtained at a ratio of 1.5, synthesizing
Na-CMC with a degree higher than 1 presented challenges. Na-CMC with such a high
degree of carboxymethylation tends to agglomerate and absorb water easily, making it
difficult to wash with an alcohol-water solvent. Moreover, laboratory conditions may
not be sufficient to remove all the water from the sample, which can cause damage to
the product.

Based on the initial goal set out in the introduction and the difficulties in handling Na-
CMC with a DS > 1, we decided to choose a ratio of 1.3 as our optimized ratio.

Figure 3.5. Sample MA4 was clumped due to water absorption during purification

41
3.1.3. Investigate the effect of molar ratio NaOH/MCA
The basis of the investigation: Change of molar ratio NaOH/MCA at the values of 2.5,
3, 3.5, 4 while keeping the NaOH concentration is 50 w/v% and the ratio
MCA/AGU=1.3 (mol/mol).

Chemicals were quantified according to Table 3.5.

Table 3.5. Study of the Influence of NaOH/MCA ratio (mol/mol)

NaOH
Sample Cotton (g) IPA (mL) MCA (g)
m (g) 𝑽𝑯𝟐 𝑶 (mL) w/v%
NM1 3 60 2.40 5 50 2.27
NM2 3 60 2.88 5.8 50 2.27
NM3 3 60 3.36 6.7 50 2.27
NM4 3 60 3.85 7.7 50 2.27

The experimental samples were analyzed and the results obtained are shown in Table
3.6 and Figure 3.3.

Table 3.6. Sample analysis results in investigating the effect of NaOH/MCA ratio
(mol/mol)

Sample NaOH/MCA (mol/mol) DS

NM1 2.5 0.404

NM2 3 0.91
NM3 3.5 0.61
NM4 4 0.474

Initially, as the molar ratio of NaOH/MCA was raised, there was a marked increase in
DS, but then it started to decline gradually. This trend may be due to the fact that a lower
ratio results in fewer hydroxide ions in the reaction solution, which in turn reduces the
number of glycosidic bonds that are broken. However, if the ratio becomes too high,
there is an excessive amount of hydroxide ions, which promotes the unwanted side effect
of MCA hydrolysis, leading to a decrease in the effectiveness of the carboxymethylation
reaction. Additionally, an excessive increment in the quantity of NaOH adversely affects

42
the reaction efficiency by causing degradation of cellulose chains during the treatment
process. This degradation leads to the disruption of crystalline regions within the
cellulose structure, ultimately resulting in the increased susceptibility of cellulose to
dissolve in the treatment solution. Consequently, the yield of cellulose fibers is reduced
[16]
.
[9]
A similar phenomenon has also been observed in another study . Although this study
was conducted under different conditions and investigated a different NaOH/MCA ratio,
a general trend emerges where the degree of Na-CMC increases with higher NaOH
concentrations. However, after reaching a certain threshold, DS begins to decline.

0.9 0.91
Degree of Substitution (DS)

0.8

0.7

0.6 0.61

0.5
0.474
0.4 0.404

0.3

0.2

0.1

0
2 2.5 3 3.5 4 4.5
NaOH/MCA (mol/mol)

Figure 3.5. The change of DS with different mole ratio NaOH/MCA

3.2. RESULTS OF THE EXPERIMENT TO DETERMINE PURIFICATION

CONDITIONS FOR NA-CMC PRODUCTION
3.2.1. Investigate the effect of washing solvent on Na-CMC purity
The basis of the investigation: Change of the EtOH concentration at the values of 70,
75, 80 %v/v while keeping the NaOH concentration is 50 w/v%, the ratio
MCA/AGU=1.3 (mol/mol) and the ratio NaOH/MCA=3 (mol/mol).

Chemicals were quantified according to Table 3.7.

Table 3.7. Study of the Influence of EtOH concentration

Sample NaOH EtOH mL/time

43
 Cotton IPA m MCA %v/v Washing
w/v%
(g) (mL) (g) (g) times
E1 3 60 3 50 2.27 70 3 100
E2 3 60 3 50 2.27 75 3 100
E3 3 60 3 50 2.27 80 3 100

The experimental samples were analyzed and the results obtained are shown in Table
3.8.

Table 3.8. Sample analysis results in investigating the effect of EtOH concentration

Sample EtOH %v/v Na-CMC (g)

E1 70 3.94
E2 75 4.11
E3 80 4.45

Under identical reaction conditions and equivalent starting material, the increase in
ethanol concentration resulted in a higher yield of Na-CMC. At an 80% concentration,
the amount of Na-CMC obtained is almost equivalent to the original cellulose in terms
of molarity, signifying a nearly 100% efficiency.

Figure 3.6. Cloudy filtrate when using washing solvents of 75% (left) and 70% (right)

In the course of washing the product, it was observed that when using ethanol
concentrations of 70% and 75%, the filtrate became turbid, indicating that some of the

44
Na-CMC had dissolved into the water during the washing process. This suggests that
Na-CMC has absorbed some of the water present in the solvent, leading to product loss.

3.2.2. Effect of washing times and washing volume on Na-CMC purity

The basis of the investigation: Change of the washing times and washing volume until
the impurity residue meet the standard, while keeping the NaOH concentration is 50
w/v%, the ratio MCA/AGU=1.3 (mol/mol), the ratio NaOH/MCA=3 (mol/mol) and
EtOH 80 %v/v.

Chemicals were quantified according to Table 3.9.

Table 3.9. Study of Influence of washing times and washing volume on purity

NaOH
Cotton IPA MCA EtOH Washing
Sample m mL/time
(g) (mL) w/v% (g) %v/v times
(g)
W1 3 60 3 50 2.27 80 3 100
W2 3 60 3 50 2.27 80 4 100
W3 3 60 3 50 2.27 80 5 100
W4 3 60 3 50 2.27 80 5 50
W5 3 60 3 50 2.27 80 6 50
W6 3 60 3 50 2.27 80 5 60

The experimental samples were analyzed and the results obtained are shown in Table
3.10.

Table 3.10. Impurities residue in CMC with various washes

EtOH Washing
Sample mL/time %NaCl %HNa
%v/v times
W1 80 3 100 5.11% 0.082%
W2 80 4 100 2.03% 0.079%
W3 80 5 100 0.62% 0.072%
W4 80 5 50 0.97% 0.076%
W5 80 6 50 0.25% 0.068%
W6 80 5 60 0.23% 0.061%

45
For sample W3 and W4, despite reducing the solvent volume used for each wash by
half, there was not a significant difference in the purity of the product. This indicates
that the number of washes has a greater impact on washing performance compared to
the volume of the solvent used. However, it is also important to note that excessive
washing is not beneficial, as demonstrated in sample W5 and W6. Using a total wash
solvent volume of 300mL, washing the product 5 times resulted in less water absorption
and a higher-quality product, while still meeting the required purity standards outlined
in the pharmacopoeia.

Therefore, with 3g of initial raw cotton, after the reaction, the purified Na-CMC product
with 80% EtOH and washed five times with 60mL each, will meet the purity standard
of the Ph.Eur 2005 pharmacopoeia

3.3. CONCLUSIONS
Based on the experimental process, the conclusions drawn regarding the factors
influencing the synthesis of Na-CMC from cotton cellulose and the purity of the product
are:

 NaOH concentration: 50 %w/v

 Molar ratio MCA/AGU: 1.3 (mol/mol)
 Molar ratio NaOH/MCA: 3 (mol/mol)
 Washing solvent: EtOH 80 %v/v
 Washing times: 5 (time)
 Washing volume/time: 60 mL

The Na-CMC product is derived from cotton material, with an ivory white color, 5.2%
moisture content, neutral pH, and it is water-soluble, forming a transparent solution
without impurities. To study the appropriate reaction process for scaling up from the
laboratory to the industrial scale, suitable research methods are undertaken.

46
 CHAPTER 4

CALCULATION AND DESIGN OF THE NA-CMC PRODUCTION

TECHNOLOGY PROCESS
4.1. BASIS OF CALCULATION
4.1.1. Calculation of the composition of the mixture after the reaction

After conducting the experiment, we deduce the following ratios:

Table 4.1. The proportions of substances before the reaction

IPA IPA IPA

Cotton NaOH H2O MCA CH3COOH
(1) (2) (3)

Mol eq. 1 4 18 - 1.3 3.5 1.76 7.77

Volum/
1 - - 20 - - - -
mass

Note that IPA (1) is the solvent for the reaction, IPA (2) is the solvent use to dissolve
MCA before adding to the reaction and IPA (3) is dilute agent for glacial CH 3COOH.

As presented in Chapter 3, after the reaction is completed, the reaction mixture needs to
be filtered to remove the IPA solvent and then washed with 80% v/v EtOH five times
for purification. Therefore, there will be a total of six filtration steps. The properties and
composition of the mixture after the first filtration is:

Table 4.2. Properties and composition of the products after the first filtration

Moisture 20.09%

%NaCl 6.23%

%HNa 0.1%

%Na-MCA 3.87%

47
 %CH3COONa 11.96%

DS 0.92

MW (=162+80×DS) 235.7557

The product, after being dried and analyzed, exhibits the following properties and
contains the following components:

Table 4.3. Properties and composition of the products after the drying process

Moisture 5.2%

%NaCl 0.23%

%HNa 0.06%

%Na-MCA 0.11%

%CH3COONa 0.13%

DS 0.92

MW (=162+80×DS) 235.7557

Base on the composition of the product after reaction, we can deduce reactions that
occurs along the conducting time:

Cellulose + NaOH → Na-Cellulose + H2O (1)

MCA + NaOH → Na-MCA + H2O (2)

Na-Cellulose + Na-MCA → Na-CMC + H2O (3)

Na-MCA + NaOH → HNa + NaCl (4)

CH3COOH + NaOH → CH3COONa + H2O (5)

We have the following mixture composition table (ignoring all off the solvent):

Table 4.4. Thành phần hỗn hợp sau phản ứng (bỏ qua dung môi)

48
 Na-CMC NaCl HNa Na-MCA CH3COONa H2O

Mol eq. 1 a b c 1.767 d

 From ion Cl- balance, we have:

a + c = 1.3 (eq.1)

 Water is produced from reactions (1), (2), (3) and (5):

d = DS + 1.3 + DS + 1.767 = 0.92×2 + 1.3 + 1.767 = 4.907 (mole)

 From ion Na+ balance, we have:

4 = DS + a + b + c + 1.76 (eq.2)

 From MCA balance, we have:

1.3 = 0.92 + c + b (eq.3)

Solving the system of equations with three unknowns above, we obtain the result:

 a = 0.93456 (mole)
 b = 0.01256 (mole)
 c = 0.36744 (mole)

Try again with balancing the masses before and after the reaction:

Before reaction: 1×162.1406 + 4×39.997 + 1.3×94.5 + 1.76×60.05 = 567.4

After reaction: 1×235.7557 + 0.93456×58.44 + 0.01256×76.05 + 0.36744×116.48 +

1.767×82.0343 + 4.907×18.01528 = 567.4

4.1.2. The overall yield of the entire system

 Designed yield: 1000 tons/year

 Number of working days: 300 days

4.1.3. Na-CMC production process

The production process of Na-CMC has been studied and simply shown by a block
diagram in Figure 4.1.

49
 Figure 4.1. Block diagram of Na-CMC production process

4.1.4. The Process Flowing Diagram (PFD)

(View in APPENDIX 2)

4.1.5. The Process and Instrumentation Diagram streamchart (P&ID).

(View in APPENDIX 2)

4.1.6. Diagram illutration

4.1.6.1. Material preparation

 Prepare a 50% w/v NaOH solution:

Solid NaOH is transported by conveyor C-01 into mixing tank R-01. Then, water is
pumped into the mixing tank using pump P-01. The liquid level in the tank is measured
by level sensor LE-01, and the signal is transmitted by level transmitter LT-01 and
displayed on level indicator control LIC-01. The signal about the liquid level in the tank
is linked to control valve CV02 to adjust the flow rate of the inlet stream. The inlet flow
rate is measured by flow sensor FE-01, and the signal is transmitted and displayed on
flow indicator control FIC-01.

50
Additionally, during the preparation of the NaOH solution, heat is generated, so the
mixing tank is cooled with cold water. The temperature of the solution is measured by
temperature sensor TE-01, and the temperature signal is transmitted using temperature
transmitter TT-01 and displayed on the temperature indicator control TIC-01. This signal
is then linked to control valve CV01 to adjust the flow rate of cold water, ensuring that
the solution's temperature remains close to 25℃

 Prepare MCA solution

MCA (solid) is transported by conveyor C-03 into mixing tank R-03. Then, IPA is
pumped into the mixing tank using pump P-03. The process of controlling the liquid
level in the tank is similar to the preparation of the 50% w/v NaOH solution.

Additionally, during the preparation of the MCA solution, it is an endothermic process,

so the mixing tank is heated with saturated steam. The temperature of the solution is
measured by temperature sensor TE-03, and the temperature signal is transmitted using
temperature transmitter TT-03 and displayed on temperature indicator control TIC-03.
This signal is then linked to control valve CV01 to adjust the amount of saturated steam,
ensuring that the solution's temperature remains close to 25℃. The temperature of the
saturated steam depends on the pressure, and in this case, we choose the steam pressure
to be at 1 bar. Therefore, the pressure of the saturated steam is measured by pressure
sensor PE-02, and the pressure signal is transmitted and displayed on pressure indicator
control PIC-02.

 Prepare CH3COOH 10%v/v solution

CH3COOH is transported into mixing tank R-04 using pump P-05. Then, IPA is
transported into the mixing tank using pump P-03. The liquid level in the mixing tank is
measured by level sensor LE-04, and the signal about the liquid level is transmitted
using level transmitter LT-04 and displayed on level indicator control LIC-04. The signal
about the liquid level will be linked to two control valves, CV08 and CV09, to adjust
the flow rates of CH3COOH and IPA, respectively.

 Prepare EtOH 80%v/v solution

51
EtOH (ethanol) 96% is transported into mixing tank R-06 using pump P-07. Then, water
is transported into the mixing tank using pump P-01. The process of controlling the
liquid level in the tank is similar to the preparation of the CH 3COOH solution.

Additionally, the preparation process will generate heat, heating up the solution, so the
mixing tank will be cooled with cold water. The process of controlling the temperature
of the solution is similar to the preparation of the 50% v/v NaOH solution.

4.1.6.2. Reactions
 Alkalization reaction

Cotton is transported into mixing tank R-02 using conveyor C-02. IPA continues to be
transported into R-02 using pump P-03. The mixture is stirred for about 30 minutes to
ensure even impregnation of the solvent into the cotton. After that, NaOH solution is
added to the mixing tank. The stirring process continues for 60 minutes to allow the
reaction to occur. The liquid level in the tank is controlled similarly to the previous
processes.

The temperature of the reaction is maintained at 35℃ using saturated steam at 1 atm,
and the temperature control is similar to the preparation process of MCA solution.

 Etherification reaction

The post-alkalization mixture is transferred into mixing tank R-05. Then, the MCA
solution is added to the mixing tank. The reaction is heated to a temperature of 65℃
using saturated steam at 1 bar. The temperature of the reaction solution is controlled
similarly to the MCA solution preparation process.

After 90 minutes, the reaction is completed, and CH3COOH solution is added to

neutralize the mixture. The liquid level in the tank is controlled similarly to the previous
processes.

4.1.6.3. Purification

After the reaction, the mixture is transferred to a centrifuge machine F-01. The filtrate
is recovered and sold to organizations for the recovery of pure IPA. The solid material
after filtration is transported using conveyor C-04 to mixing tank R-07 for purification
using the washing method with 80% v/v EtOH. The liquid level in the tank is controlled

52
similarly to the previous processes. Then, the mixture is filtered again using the
centrifuge and washed four more times.

After thorough washing to remove impurities, the product is transferred to fluidized bed
dryers D-01 and D-02 using conveyor C-09. Two dryers are used as the product is dried
in batches. While one dryer is being loaded, the other dryer will be in operation for
drying.

Finally, the dried product is finely ground using a ball mill M-01 and then packaged.
The EtOH solution after washing is collected in tank T-01 and then subjected to
distillation using distillation column TC-01 to recover 96% EtOH.96%.

4.1.7. Materials balance

Calculate the material balance with a production rate of 1000 tons of Na-CMC per year.

The average number of working days in a year is 300 days. The production rate of the
product is calculated per hour as:

×
𝐺 =𝐺 = = 138.88 (kg/h)
×

Assuming all inputs are at 25℃, we calculate the following streams:

 Stream 24

The product after drying has a moisture content of 5.2% (Table 4.3). The amount of
water present in the product is:

= 5.2% → 𝐺 = 7.22 (kg/h)

Using the analytical method, the amount of Na-MCA present in the product is
determined to be 0.11% (Table 4.3):

𝐺 = 0.11% × 𝐺 = 0.1527 (kg/h)

Similarly, the amounts of NaCl, HNa, and CH 3COONa in the product are as follows:

𝐺 = 0.23% × 𝐺 = 0.3914 (kg/h)

𝐺 = 0.06% × 𝐺 = 0.0833 (kg/h)

𝐺 = 0.13% × 𝐺 = 0.1805 (kg/h)

53
Because the cotton raw material contains impurities, specifically in this study, I stipulate
that the impurity level is 6% according to reference [1]:

𝑛 = × . = 0.532 (kmol/h)
.

× × .
𝐺 = = 5.51 (kg/h)
.

𝐺 =𝑀 ×𝑛 = 125.42 (kg/h)

 Stream 4

𝐺 =𝑀 ×𝑛 = 86.26 (kg/h)

𝐺 =𝐺 = 5.51 (kg/h)

𝐺 =𝐺 +𝐺 = 91.77 (kg/h)

 Stream 1

Based on the investigation in Chapter 3, the conclusion drawn is that the molar ratio of
NaOH to AGU is 4 (mol/mol).

𝑛 =𝑛 × 4 = 2.128 (kmol/h)

𝐺 =𝑛 ×𝑀 = 85.12 (kg/h)

 Stream 2

The concentration of NaOH used is 50% w/v:

𝑉 = = 170.24 (L/h)
.

𝐺 =𝑉 ×𝑑 = 169.72 (kg/h)

 Stream 5

The solvent used in the reaction is IPA with a purity of 99.97%. The ratio of IPA used is
20 times the volume of the cotton's weight:

𝑉 =𝐺 × 20 × 0.9997 = 1834.78 (L/h)

𝐺 =𝑉 ×𝑑 = 1355.69 (kg/h)

𝑉 =𝐺 × 20 − 𝑉 = 0.5506 (L/h)

𝐺 =𝑉 ×𝑑 = 0.5489 (kg/h)
54
 Stream 7

Based on the investigation in Chapter 3, the conclusion drawn is that the molar ratio of
MCA to AGU is 1.3 (mol/mol).

𝑛 =𝑛 × 1.3 = 0.6916 (kmol/h)

𝐺 =𝑛 ×𝑀 = 65.36 (kg/h)

 Stream 6

MCA is dissolved in IPA with a concentration of 4.81 × 10-3 kmol/L.

𝑉 =𝑛 × 0.9997/(4.81 × 10 ) = 143.74 (L/h)

𝐺 =𝑉 ×𝑑 = 112.98 (kg/h)

× .
𝑉 = = 0.0431 (L/h)
.

𝐺 =𝑉 ×𝑑 = 0.043 (kg/h)

 Stream 9

According Table 4.1, we have:

𝑛 =𝑛 × 1.76 = 0.9403 (kmol/h)

𝐺 =𝑛 ×𝑀 = 56.46 (kg/h)

𝑉 = = 60.05 (L/h)

 Stream 8

Dilute CH3COOH with IPA to form a solution with a volume concentration of 10% v/v

𝑉 = −𝑉 × 0.9997 = 540.29 (L/h)

%

𝐺 =𝑉 ×𝑑 = 424.67 (kg/h)

× .
𝑉 = = 0.1621 (L/h)
.

𝐺 =𝑉 ×𝑑 = 0.1616 (kg/h)

 Stream 12

55
Assuming there are n OH- groups in cellulose that react with NaOH, there will be n
carboxymethyl groups substituting the OH- groups. Therefore, in the alkalization
reaction, NaOH will lose an equivalent number of moles as the DS of Na-CMC:

𝑛 =𝑛 − 𝐷𝑆 × 𝑛 = 1.638 (kmol/h)

𝐺 =𝑛 ×𝑀 = 65.53 (kg/h)

𝐺 =𝐺 = 5.51 (kg/h)

𝐺 =𝑛 ×𝑀 = 97.02 (kg/h)

𝐺 =𝐺 = 1355.69 (kg/h)

The water in stream 12 will be equal to the sum of the water in stream 5 and the water
in stream 2, along with the water produced from the alkalization reaction.:

𝐺 =𝐺 +𝐺 +𝑀 × 𝐷𝑆 × 𝑛 = 179.009 (kg/h)

 Stream 13

According to part 4.1.1, we have:

Table 4.5. Full composition of the reaction mixture (excluding solvent)

Na-CMC NaCl HNa Na-MCA CH3COONa H2O

Mol eq. 1 0.9326 0.01256 0.3674 1.767 4.907

𝐺 =𝑛 ×𝑀 = 125.42 (kg/h)

𝐺 =𝐺 = 5.51 (kg/h)

𝐺 =𝑛 ×𝑀 = 77.14 (kg/h)

𝐺 =𝑛 × 0.9326 × 𝑀 = 28.994 (kg/h)

𝐺 =𝑛 × 0.3674 × 𝑀 = 22.7698 (kg/h)

𝐺 =𝑛 × 0.01256 × 𝑀 = 0.50813 (kg/h)

56
The water in stream 13 will consist of the water from stream 12, stream 6, stream 8, and
the water produced from reactions (2), (3), and (5).

𝐺 =𝐺 +𝐺 +𝐺 + (𝑛 + 𝐷𝑆 × 𝑛 +𝑛 )×𝑀 =
208.61 (kg/h)

The IPA in stream 13 will consist of the IPA from stream 12, stream 6, and stream 8

𝐺 =𝐺 +𝐺 +𝐺 = 1893.34 (kg/h)

 Stream 17

After the first filtration to remove the IPA solvent, we have the composition table of the
mixture (Table 4.2):

Table 4.2. Properties and composition of the products after the first filtration

Moisture 20.09%

%NaCl 6.23%

%HNa 0.1%

%Na-MCA 3.87%

%CH3COONa 11.96%

DS 0.92

MW (=162+80×DS) 235.7557

𝐺 =𝐺 = 125.42 (kg/h)

𝐺 =𝐺 = 5.51 (kg/h)

The percentage of Na-CMC and impurities in stream 17 is:

1 - %NaCl(17) - %HNa(17) - %Na-MCA(17) - %CH 3COONa(17) -%H2O (17) =

57.75%

𝐺 = = 226.72 (kg/h)
.

57
𝐺 =𝐺 × %CH3COONa(17) = 27.116 (kg/h)

𝐺 =𝐺 × %HNa(17) = 0.2267 (kg/h)

𝐺 =𝐺 × %NaCl(17) = 14.125 (kg/h)

𝐺 =𝐺 × %Na − MCA(17) = 8.774 (kg/h)

Assuming the water and IPA ratio after filtration is the same as the water and IPA ratio
in stream 13:

𝑟 (17) = = 9.07

× .
𝐺 = = 4.52 (kg/h)
( )

𝐺 =𝐺 × 0.2009 − 𝐺 = 41.027 (kg/h)

 Stream 16

In Chapter 3, it was determined that with an input of 3g of cotton, the product needs to
be washed 5 times, with each washing using 60mL of 80% v/v EtOH. Therefore, when
scaling up to a 1000 tons/year production scale, the solvent requirement for washing in
one hour would be:

𝑉 % =𝐺 × 20 × 5 = 9176.65 (L/h)

𝐺 % =𝑉 % ×𝑑 % = 7885.22 (kg/h)

 Stream 15

%× .
𝑉 % = = 7647.2 (L/h)
.

𝐺 % =𝑉 % ×𝑑 % = 6194.24 (kg/h)

 Stream 14

𝐺 =𝐺 % −𝐺 % = 1690.98 (kg/h)

𝑉 = = 1690.07 (L/h)

 Stream 18

Stream 18 is the output after all 5 washes with 80% v/v EtOH

58
𝑉 =𝑉 % × 0.96 = 7341.32 (L/h)

𝐺 =𝑉 ×𝑑 = 5792.3 (kg/h)

𝐺 =𝐺 % −𝐺 +𝐺 = 2097.44 (kg/h)

𝑉 = = 2103.75 (L/h)

𝐺 =𝐺 = 41.027 (kg/h)

𝑉 = = 52.198 (L/h)

𝐺 =𝐺 = 14.125 (kg/h)

𝐺 =𝐺 = 0.2267 (kg/h)

𝐺 =𝐺 = 8.774 (kg/h)

𝐺 =𝐺 = 27.116 (kg/h)

𝐺 =𝐺 = 125.425 (kg/h)

𝐺 =𝐺 = 5.51 (kg/h)

 Stream 23

After completing 5 rounds of washing with 80% v/v EtOH, the mixture will undergo a
6th filtration. The mixture after the 6th filtration will have a moisture content of 20%
(equivalent to the moisture content after the first filtration as both are filtered using a
centrifuge). The composition of the mixture will be similar to the mixture after drying
(stream 24).

𝐺 =𝐺 = 0.3194 (kg/h)

𝐺 =𝐺 = 0.0833 (kg/h)

𝐺 =𝐺 = 0.1528 (kg/h)

𝐺 =𝐺 = 0.1806 (kg/h)

𝐺 =𝐺 = 125.425 (kg/h)

𝐺 =𝐺 = 5.51 (kg/h)

59
Assuming there is no IPA left in the mixture, and the volume ratio of water to EtOH
after pressing is approximately the same as the ratio in the washing solvent.

×
= → =
×

𝐺 = = 164.58 (kg/h)
.

𝐺 =𝐺 × 20% = 32.917 (kg/h)

𝐺 = × = 7.902 (kg/h)

𝐺 =𝐺 −𝐺 = 25.014 (kg/h)

 Stream 20

Feed for Ethanol Recovery Distillation:

𝐺 =𝐺 −𝐺 = 5767.29 (kg/h)

𝐺 =𝐺 = 41.028 (kg/h)

𝐺 =𝐺 −𝐺 = 13.8052 (kg/h)

𝐺 =𝐺 −𝐺 = 0.1434 (kg/h)

𝐺 =𝐺 −𝐺 = 13.8052 (kg/h)

𝐺 =𝐺 −𝐺 = 26.935 (kg/h)

𝐺 =𝐺 −𝐺 = 8.621 (kg/h)

 Stream 22

I am using Aspen Plus V11 to simulate the process of ethanol recovery distillation. The
inputs I have entered into Aspen Plus are as follows:

 Basic method: ELECNRTL

 Input for the heat exchanger equipment HEATX:
Total mass = 7947.36 (kg/h)

Mass fraction (F1)

H2O EtOH IPA NaCl HNa CH3COONa Na-MCA
0.262922258 0.7256862 0.005162 0.001737 1.8E-05 0.00338919 0.001084797
 Input for the RADFRAC equipment

60
 Reflux ratio: 2.92803
Composition EtOH
Light key
Recovery 0.8
Composition H2O
Heavy key
Recovery 0.11629

The simulation results are presented in Figure 4.2:

Figure 4.2. Simulation results of EtOH recovery using Aspen Plus V11

RADFRAC equipment is a tray column with a total of 8 trays (including the reboiler
and condenser), with the feed stage located on tray number 5.

Figure 4.3. RADFRAC equipment of EtOH recovery process

61
𝐺 = 5458.33 (kg/h)

𝐺 = 5173.6551 (kg/h)

𝑉 = = 6557.23 (L/h)

𝐺 = 275.798 (kg/h)

𝑉 = = 276.628 (L/h)

𝐺 = 8.8768 (kg/h)

𝑉 = = 11.2937 (L/h)

%EtOH (22) = × 100 = 95.7937 %𝑣/𝑣

 Stream 19

Feed for IPA Recovery Distillation

𝐺 =𝐺 −𝐺 = 1852.31 (kg/h)

𝑉 = = 2356.63 (L/h)

𝐺 =𝐺 −𝐺 = 204.09 (kg/h)

𝑉 = = 204.706 (L/h)

𝐺 =𝐺 −𝐺 = 0.2814 (kg/h)

𝐺 =𝐺 −𝐺 = 14.869 (kg/h)

𝐺 =𝐺 −𝐺 = 50.021 (kg/h)

𝐺 =𝐺 −𝐺 = 13.996 (kg/h)

%IPA (19) = = 90 %𝑤/𝑤

 Stream 21

Under standard atmospheric conditions, a mixture of IPA and water forms a uniform,
lowest-boiling azeotrope at a concentration range of 87.4% to 87.7% by mass and boils
at temperatures between 80.3°C and 80.4°C [17].

62
Stream 19 shows that the mass percentage of IPA is 90%; therefore, it is not possible to
recover more IPA through distillation.

In this case, my choice is to sell the 90% IPA (in stream 19) to organizations with the
capability and equipment to purify the IPA back to its original purity level of 99.97%.

As a result, stream 21 and stream 19 are identical.

 Thus, we have the material balance table as follows:

Table 4.6. The material balance table of the Na-CMC production process

Stream 1 2 3 4
Cellulose (kg/h) - - - 86.26053
Impurity (kg/h) - - - 5.505991
NaOH (kg/h) 85.1153223 - 85.1153223 -
H2O (kg/h) - 169.7199527 169.7199527 -
IPA (kg/h) - - - -
MCA (kg/h) - - - -
Na-MCA (kg/h) - - - -
Na-Cellulose (kg/h) - - - -
CH3COOH (kg/h) - - - -
NaCl (kg/h) - - - -
HNa (kg/h) - - - -
EtOH (kg/h) - - - -
Na-CMC (kg/h) - - - -
CH3COONa (kg/h) - - - -
Total 85.1153223 169.7199527 254.835275 91.76652

Table 4.6. The material balance table of the Na-CMC production process (continues)

Stream 5 6 7 8
Cellulose (kg/h) - - - -
Impurity (kg/h) -
NaOH (kg/h) - - - -

63
 H2O (kg/h) 0.54894732 0.043006592 - 0.161648595
IPA (kg/h) 1355.690857 112.9824148 - 424.6662619
MCA (kg/h) - - 65.35751022 -
Na-MCA (kg/h) - - - -
Na-Cellulose (kg/h) - - - -
CH3COOH (kg/h) - - - -
NaCl (kg/h) - - - -
HNa (kg/h) - - - -
EtOH (kg/h) - - - -
Na-CMC (kg/h) - - - -
CH3COONa (kg/h) - - - -
Total 1356.239805 113.0254214 65.35751022 424.8279105

Table 4.6. The material balance table of the Na-CMC production process (continues)

Stream 9 10 11 12
Cellulose (kg/h) - - - -
Impurity (kg/h) 5.505991
NaOH (kg/h) - - - 65.5388
H2O (kg/h) - 0.161648595 0.043006592 179.009
IPA (kg/h) - 424.6662619 112.9824148 1355.691
MCA (kg/h) - - 65.35751022 -
Na-MCA (kg/h) - - -
Na-Cellulose (kg/h) - - - 97.01958
CH3COOH (kg/h) 56.46485969 56.46485969 - -
NaCl (kg/h) - - - -
HNa (kg/h) - - - -
EtOH (kg/h) - - - -
Na-CMC (kg/h) - - - -
CH3COONa (kg/h) - - - -
Total 56.46485969 481.2927702 178.3829316 1702.764

64
Table 4.6. The material balance table of the Na-CMC production process (continues)

Stream 13 14 15 16
Cellulose (kg/h) - - - -
Impurity (kg/h) 5.505991178
NaOH (kg/h) - - - -
H2O (kg/h) 208.6129999 1690.981657 247.769603 1938.751
IPA (kg/h) 1893.339534 - - -
MCA (kg/h) - - - -
Na-MCA (kg/h) 22.76979955
Na-Cellulose (kg/h) - - - -
CH3COOH (kg/h) - - - -
NaCl (kg/h) 28.99391798 - - -
HNa (kg/h) 0.508133426 - - -
EtOH (kg/h) - - 5946.470473 5946.47
Na-CMC (kg/h) 125.4245644 - - -
CH3COONa (kg/h) 77.13664012 - - -
Total 2362.291581 1690.981657 6194.240076 7885.222

Table 4.6. The material balance table of the Na-CMC production process (continues)

Stream 17 18 19 20
Cellulose (kg/h) - - - -
Impurity (kg/h) 5.505991178 5.505991178 - -
NaOH (kg/h) - - - -
H2O (kg/h) 4.520509879 2097.439523 204.09249 2089.5373
IPA (kg/h) 41.02745308 41.02745308 1852.31208 41.0275
MCA (kg/h) - - - -
Na-MCA (kg/h) 8.774047619 8.774047619 13.9957519 8.621269841
Na-Cellulose (kg/h) - - - -
CH3COOH (kg/h) - - - -
NaCl (kg/h) 14.12462963 14.12462963 14.8692884 13.8052

65
 HNa (kg/h) 0.226719577 0.226719577 0.28141385 0.1434
EtOH (kg/h) - 5792.30272 - 5767.2883
Na-CMC (kg/h) 125.4245644 125.4245644 - -
CH3COONa (kg/h) 27.11566138 27.11566138 50.0209787 26.9351
Total 226.7195767 8111.94131 2135.572 7947.357976

Table 4.6. The material balance table of the Na-CMC production process (continues)

Stream 21 22 23 24
Cellulose (kg/h) - - - -
Impurity (kg/h) - 5.505991178 5.505991178
NaOH (kg/h) - - - -
H2O (kg/h) 204.09249 275.798032 7.902219279 7.222222222
IPA (kg/h) 1852.31208 8.876812708 - -
MCA (kg/h) - - - -
Na-MCA (kg/h) 13.9957519 0.152777778 0.152777778
Na-Cellulose (kg/h) - - - -
CH3COOH (kg/h) - - - -
NaCl (kg/h) 14.8692884 - 0.319444444 0.319444444
HNa (kg/h) 0.28141385 - 0.083333333 0.083333333
EtOH (kg/h) - 5173.655155 25.01444739 -
Na-CMC (kg/h) - - 125.4245644 125.4245644
CH3COONa (kg/h) 50.0209787 - 0.180555556 0.180555556
Total 2135.572 5458.33 164.5833333 138.8888889

66
4.2. CALCULATE FOR THE EQUIPMENT OF NA-CMC SYNTHESIS
PROCESS

Here, the etherification reaction is selected for detailed design of the reaction equipment.

4.2.1. Heat balances

Phương trình cân bằng nhiệt lượng:

𝑄 + 𝑄 + ∆𝑄 = 𝑄 + 𝑄 (5)

Where:

𝑄 : Heat carried by the material into the equipment (kJ/h)

𝑄 : Heat carried by the product out of the equipment (kJ/h)

𝑄 : Heat produced by a chemical reaction (kJ/h)

𝑄 : Heat loss by the environment (kJ/h)

∆𝑄: Heat supplied by the heat carrier (kJ/h)

In addition to the five mentioned heat inputs, there is also heat generated by stirring,
friction of the solution with the agitator and baffles, but we will neglect this heat.
Furthermore, due to the complex composition and small mass of impurities (compared
to the entire system), I will disregard the heat contribution from impurities brought into
and removed from the equipment.

Before calculating the heat content for the reaction equipment, we need to have the
specific heat capacity of the reactants and products of the reaction. The specific heat
capacity of chemical compounds can be calculated using the following formula [18]:

𝑀 × 𝐶 = 𝑛 ×𝐶 + 𝑛 × 𝐶 +⋯+𝑛 ×𝐶 (6)

Where:

M: Molar mass of the compound (kg/kmol)

C: Specific heat capacity of the compound (kJ/kg℃)

𝑛 , 𝑛 , … 𝑛 : The number of atoms of the elements in the compound

𝐶 , 𝐶 , … 𝐶 : The atomic heat capacity of the respective elements (kJ/kg℃)

67
In fact, the specific heat capacity of the atoms is a function of temperature. However, in
this calculation, the difference in specific heat capacity between different temperatures
is not significant and should be ignored.

Table 4.7. Specific heat capacity of the elements (kJ/kg℃) [18] [20]

Carbon (C) Hydro (H) Oxygen (O) Chloro (Cl) Sodium (Na)
C (solide) 7.5 9.63 16.8 - 152
C (liquid) 11.7 18 25.1 33.5 172.5

Thus, based on the specific heat of atoms in Table 4.7, it is easy to calculate the specific
heat of the compounds in the reaction. The specific heat capacities of the compounds
are shown in the following table:

Table 4.8. Specific heat capacity of the compounds in the synthesis of Na-CMC

Specific heat
No. Name Formula State
(kJ/kg℃)
1 Na - cellulose C6H9O5Na solid 2.128
2 Sodium hydroxide NaOH liquid 4.877
3 Water H2 O liquid 3.391
4 IPA C3H8O liquid 3.397
5 MCA C2H3O2Cl liquid 1.704
6 Acid acetic C2H4O2 liquid 2.424
7 Na - MCA C2H2O2NaCl liquid 2.533
8 Sodium chloride NaCl liquid 3.173
9 Sodum glycolate C2H4O3 liquid 2.244
10 Na - CMC C8H11O7Na solid 3.635
11 Sodium acetate C2H3O2Na liquid 3.408

4.2.1.1. Heat carried by the material into the equipment 𝑸𝟏

The heat carried by the material is calculated by the formula:

𝑄 = ∑𝐺 × 𝐶 × 𝑇 (7)

Where:

Q: Heat carried by the material into the equipment (kJ/h)

G: Mass of material entering the equipment (kg/h)

68
Cp: Specific heat capacity of the material (kJ/kg℃)

T: Material temperature entering the equipment

The temperatures of the input materials are assumed to be 25℃ (298K). The
neutralization reaction of CH3COOH occurs after the etherification reaction and does
not affect the reaction temperature, so we do not consider it in the heat balance.
Therefore, we have the following table:

Table 4.9. The list of input materials for the synthesis of Na-CMC

STT Name Flowrate (kg/h) Specific heat (kJ/kg℃)

1 Na-Cellulose 97.020 2.128
2 NaOH 65.538 4.877
3 H2O 179.214 3.391
4 IPA 1893.34 3.397
5 MCA 65.358 1.704

In this way, we can calculate the heat content from the incoming raw materials as
follows:

𝑄 = (𝐺 ×𝐶 +𝐺 ×𝐶 +𝐺 ×𝐶 +𝐺 ×
𝐶 +𝐺 ×𝐶 ) × 298 = 2288156.724 (kJ/h)

4.2.1.2. Heat carried by the product out of the equipment 𝑸𝟐

Similarly to the calculation of 𝑄 , the neutralization reaction of CH3COOH occurs after

the etherification reaction and does not affect the reaction temperature. The temperatures
of the output products are the same as the temperature of the etherification reaction,
which is 65℃ (338K). Therefore, we have the following table:

Table 4.10. The list of output products of the synthesis reaction of Na-CMC

STT Name Flowrate (kg/h) Specific heat (kJ/kg℃)

1 H2O 208.613 3.391
2 IPA 1893.340 3.397
3 Na-MCA 22.770 2.533
4 NaCl 28.993 3.173
5 HNa 0.5081 2.244

69
 6 Na-CMC 125.425 3.635

In this way, we can calculate the heat content carried away by the products as follows:

𝑄 = (𝐺 ×𝐶 +𝐺 ×𝐶 +𝐺 ×𝐶 +𝐺 ×𝐶 +𝐺 ×
𝐶 +𝐺 ×𝐶 ) × 338 = 2618602.409 (kJ/h)

4.2.1.3. Heat produced by chemical reaction 𝑸𝟑

There are 3 reactions of interest in the process of calculating the heat content for the
equipment:

MCA + NaOH → Na-MCA + H2O (2)

Na-Cellulose + Na-MCA → Na-CMC + H2O (3)

Na-MCA + NaOH → HNa + NaCl (4)

 Reaction (2)

The enthalpy of reaction (2) is calculated based on the heat of formation of the reactants
and products. We have the following formula:

ΔH_rxn = Σ(nΔHf(products)) − Σ(mΔHf(reactants)) (8)

Where:

ΔH_rxn: Enthalpy of reaction (kJ/h)

ΔHf(products): Heat of formation of product (kJ/kmol.h)

n: Moles of product (kmol)

ΔHf(reactants): Heat of formation of reactant (kJ/kmol.h)

m: Moles of reactant (kmol)

We have the heat of formation for the reactants and products as follows:

Table 4.11. Heat of formation of reactants and product in reaction (2)

No. Name ΔHf (kJ/kmol)

1 NaOH -469415
2 MCA -4090100
3 Na-MCA -419200

70
 4 H2O -241826.1

With reaction (2), we observe that NaOH is in excess, and all MCA will be converted to
Na-MCA. Therefore, the number of moles of the reactants and products will be taken
equal to the number of moles of MCA. The enthalpy of reaction (2) is calculated as
follows:

ΔH_rxn(2) = (ΔHf(Na − MCA) + ΔHf(H2O) − ΔHf(MCA) − ΔHf(NaOH)) ×

= 206439.0617 (kJ/h)

 Reaction (3)

To calculate the heat content generated by reaction (3), we rely on the energy of the
chemical bonds involved. The reaction involves the breaking of two bonds, O-Na bond
and C-Cl bond, while simultaneously forming two new bonds, Na-Cl bond and C-O
bond. We have the table of bond energies as follows:

Bảng 4.12. Energies of some chemical bonds [21]

Bond C-Cl C-O Na-Cl O-Na

Energy (kJ/mol) 293 358 410 257

The enthalpy of reaction will be calculated based on the number of moles of Na-CMC.
Therefore, the enthalpy of reaction (3) is calculated as follows:

ΔH_rxn(3) = ΔH ( ) = (𝐸 +𝐸 −𝐸 −𝐸 )× =

−115978.325 (kJ/h)

 Reaction (4)

The enthalpy of reaction (4) is calculated based on the heat of formation of the
substances involved in the reaction, and it is also calculated using equation (8). We have
the heat of formation for the reactants and products as follows::

Table 4.13. Heat of formation of reactants and product in reaction (4)

No. Name ΔHf (kJ/kmol)

1 NaOH -469415
2 Na-MCA -419200

71
 3 HNa -583000
4 NaCl -1296703.8

The enthalpy of reaction will be calculated based on the number of moles of HNa.
Therefore, the enthalpy of reaction (4) is calculated as follows:

ΔH_rxn(4) = ΔHf(HNa) + ΔHf(NaCl) − ΔHf(Na − MCA) − ΔHf(NaOH) ×

= −6622.030 (kJ/h)

So, the heat content generated by the chemical reaction is:

𝑄 = ΔH ( ) + ΔH ( ) + ΔH ( ) = 83838.707 (kJ/h)

4.2.1.4. Heat loss by the environment 𝑸𝟒

Accepts heat loss to the surrounding environment equal to 5% of the heat carried by
the product out of the equipment:

𝑄 = 5% × 𝑄 = 130930.1 (kJ/h)

4.2.1.5. Heat supplied by the heat carrier 𝚫𝐐

According to equation (5) we have:

ΔQ = 𝑄 + 𝑄 − (𝑄 + 𝑄 ) = 377547.1 (kJ/h) > 0

Thus, using the heat carrier as the heating agent. We choose saturated steam as the heat
carrier in this case.

4.2.2. Detailed calculation of Na-CMC synthesis reactor

4.2.2.1. Process Technology Parameters

From the experimental results and material balance calculations, the following process
technology parameters have been determined:

Table 4.14. The process technology parameters for the reaction equipment

Mass
Symbol Unit
flowrate

Flowrate

Alkalization mixture G12 1702.764232 kg/h

72
 MCA
G11 178.3829316 kg/h
4.81 × 10-3 kmol/L

CH3COOH 10%v/v G10 481.2927702 kg/h

Product (liquid + solid) G13 2362.291581 kg/h

Reaction conditions

𝑇 25 ℃
Temperature
𝑇 65 ℃

NaOH + MCA → Na-MCA + H2O

Na-Cellulose + Na-MCA → Na-CMC + NaCl

Reaction
NaOH + Na-MCA → NaH + NaCl

NaOH + CH3COOH → CH3COONa + H2O

Reaction time 𝑡 90 phút

Degree of Substitution DS 0.92

To have a complete set of process technology parameters for detailed calculations of the
reaction equipment, we need to calculate the density and viscosity of the streams
involved.

 Density

Density of a mixture is calculated using the formula:

=∑ (9)

Where:

𝑥 : Mass fraction concentration of each component

𝜌 : Density of each component

Bảng 4.15. Components of stream 12

𝝆𝒊 𝒙𝒊
Components Flowrate (kg/h) 𝒙𝒊
(kg/m3) 𝝆𝒊

73
 Impurities 5.506 0.00323 1048.67 3.0835× 10
NaOH 65.539 0.0385 2130 1.807 × 10
H2O 179.009 0.1051 997 0.0001054
IPA 1355.691 0.7962 786 0.001013
Na-Cellulose 97.02 0.0570 1582 3.6016× 10
∑= 0.0011755

→ Density of stream 12:

𝜌 = = 850.662 (kg/m3)
∑

Bảng 4.16. Components of stream 11

𝝆𝒊 𝒙𝒊
Components Flowrate (kg/h) 𝒙𝒊
(kg/m3) 𝝆𝒊

MCA 63.358 0.3664 1580 0.000232

IPA 112.982 0.6334 786 0.000806
H2O 0.043 0.000241 997 2.418 × 10
∑= 0.00104

→ Density of stream 11:

𝜌 = = 963.44 (kg/m3)
∑

Bảng 4.17. Components of stream 10

𝝆𝒊 𝒙𝒊
Components Flowrate (kg/h) 𝒙𝒊
(kg/m3) 𝝆𝒊

CH3COOH 56.465 0.1173 1049 0.0001118

IPA 424.666 0.8823 786 0.001123
H2O 0.1616 0.000335 997 3.368 × 10
∑= 0.001234

→ Density of stream 10:

𝜌 = = 809.879 (kg/m3)
∑

Bảng 4.18. Components of stream 13

74
 𝝆𝒊 𝒙𝒊
Components Flowrate (kg/h) 𝒙𝒊
(kg/m3) 𝝆𝒊

Tạp 5.506 0.00233 1048.67 2.222 × 10

H2O 208.613 0.0883 997 8.857 × 10
IPA 1893.34 0.8015 786 0.0010197
Na-MCA 22.77 0.00964 1870 5.154 × 10
NaCl 28.994 0.01227 2160 5.682 × 10
HNa 0.5081 0.000215 1490 1.444 × 10
Na-CMC 125.425 0.05309 520 0.000102105
CH3COONa 77.137 0.0327 1530 2.134 × 10
∑= 0.001245

→ Density of stream 13:

𝜌 = = 803.261 (kg/m3)
∑

 Viscosity

We will focus on calculating the viscosity for the mixture before the reaction. Once
again, CH3COOH is a neutralizing agent and used after the etherification reaction, so it
will not be considered in the pre-reaction mixtures.

The volume fraction of the solid phase in the pre-reaction mixture can be calculated
using the following formula:

𝐺
𝑑
𝜑 = × 100% = 2.2%
𝐺 𝐺 𝐺
+ +
𝜌 𝜌 𝜌

If the volume fraction of the solid phase in the mixture is less than 10%, then the
viscosity of the mixture can be calculated using the formula for dilute suspensions, as
described in reference [18]:

𝜇 = 𝜇 × (1 + 2.5 × 𝜑) (10)

Where:

𝜇 : Dynamic viscosity of the medium (N.s/m2)

75
𝜑 : Concentration of solid phase in suspension, by volume fraction

The environment in the pre-reaction mixture is a mixture of various substances. We

have the formula for calculating viscosity as follows [18]:

𝑙𝑔𝜇 = 𝑥 𝑙𝑔𝜇 + 𝑥 𝑙𝑔𝜇 + ⋯ (11)

Where:

𝜇 , 𝜇 : Dynamic viscosity of the components (cP)

𝑥 , 𝑥 : Molar concentrations of the components in the mixture

Table 4.19. The composition of the mixture before the reaction

Components NaOH IPA H2O MCA

Flowrate (kg/h) 65.539 1468.673 179.052 65.358
Mole fraction 0.0446 0.6657 0.2708 0.0188
Viscosity (cP) [18] [20] 1.1721 2.44 1 1.0562

→𝜇 = 1.8257 (𝑐𝑃) = 0.0018257 𝑁. 𝑠/𝑚

So the viscosity of the suspension before the reaction is:

𝜇 =𝜇 × (1 + 2.5 × 𝜑 ) = 1.9263 𝑐𝑃 = 0.019263 𝑃 =

0.001926 𝑁. 𝑠/𝑚

4.2.2.2. Preliminary equipment sizing calculation for the reaction equipment.

The ideal continuous stirred tank reactor (CSTR) operates with uniform concentration
at all positions and times, and the concentration is equal to the concentration of the
product. The volumetric flow rate of the reaction mass is calculated based on the
volumetric flow rate of the product:

𝑉 = = 2.9409 (m3/h)

The required reaction time to achieve the desired conversion is 90 minutes, so the
reaction volume is calculated as follows:

𝑉 =𝑉 × = 4.4113 (m3/h)

Assuming the containment factor is 0.6, the volume of the reaction tank can be
calculated as:

76
 𝑉 = = 7.3522 (m3/h)
.

Considering the volume of the equipment as a cylindrical shape with a height H and an
internal diameter Dt, and choosing the ratio H/Dt = 1.5, the internal diameter Dt is
calculated as follows:

𝑉 ×4
𝐷𝑡 = = 1.8411 (𝑚)
𝐻
𝜋×
𝐷𝑡

Choose Dt = 1.9 m → H = 1.5 × Dt = 2.9 (m)

With equipment having such dimensions, the liquid level in the vessel will have a
height of approximately 1.55 m. Let's consider this as h c = 1.6 m.

Select equipment bottom height ℎ = 0.4 (𝑚)

The height of the non-heated empty space above is approximately h0 = 0.5 (m)

4.2.2.3. Calculate the thickness of the vessel wall

Hydrostatic pressure at the bottom of the tank:

𝑃 =𝜌 × 𝑔 × ℎ = 12607.98 N/m2

Where:

𝜌 : Density of the product mixture (kg/m3)

𝑔 : Gravity acceleration, g = 9.81 (m/s2)

ℎ : Liquid column height in the equipment (m)

Pressure in the equipment:

𝑃 =𝑃 +𝑃 = 113032.98 (N/m2)

Where:

𝑃 : Atmospheric pressure, 𝑃 = 101325 (N/m2)

Therefore, the reaction equipment will operate at pressures lower than 1.6.10 6 N/m2, and
it will have a cylindrical welded vessel. Due to the process involving Na-CMC
production in the pharmaceutical industry, the reaction takes place at high temperatures
and involves acidic components. Thus, it is essential to choose a material that meets all
these requirements. For this purpose, I have chosen stainless steel 316 because it has a
77
high chromium and nickel content, making it capable of withstanding high temperatures,
resisting acids, alkalis, and especially environments with high chloride concentrations,
such as salt solutions.

 The thickness of the cylindrical vessel wall to withstand the working pressure is
calculated using the following formula [19]:
×
𝑆= +𝐶 (12)
×[ ]×

Where:

Dt : Inner diameter of equipment (m)

𝑃 : Pressure in the equipment (N/m2)

[𝜎] : The allowable stress on the vessel's body (N/m2)

𝜑 : The weld joint strength coefficient.

C: The thickness allowance coefficient (m)

Because the material we have chosen for designing the equipment is stainless steel 316,
we have the following parameters [22]:

 The allowable tensile stress 𝜎 = 515. 10 N/m2

 The allowable compressive stress 𝜎 = 205. 10 N/m2

The values of the safety factor for stainless carbon steel manufactured by rolling and
forging methods are as follows [19]:

 The safety factor based on the tensile limit 𝑛 = 2.6

 The safety factor based on the yield limit 𝑛 = 1.5

With equipment operating at low pressure, not containing hazardous explosive

materials, and not being directly exposed to open flames, gas furnaces, or electric
resistors, the adjustment factor is 𝜂 = 1 [19]

The allowable stress of the material based on the ultimate strength limit [19]:

[𝜎 ] = × 𝜂 = 198.1 × 10 (N/m2)

The allowable stress of the material based on the yield strength limit [19]:

[𝜎 ] = × 𝜂 = 136.67 × 10 (N/m2)

78
→ [𝜎] = min([𝜎 ] , [𝜎 ]) = 136.67 (N/m2)

Select manual electric arc welding technique for the equipment made of stainless steel
with Dt > 0.7m, and the weld joint strength coefficient φ = 0.95. [19]

The additional thickness due to corrosion is calculated using the following formula [19]

𝐶 =𝐶 +𝐶 +𝐶 (13)

Where:

𝐶 : The additional thickness coefficient due to corrosion. For durable materials like
stainless steel 316, 𝐶 = 1 (𝑚𝑚) [19]

𝐶 : The additional thickness coefficient due to erosion. In this case, we can ignore 𝐶

𝐶 : The additional thickness coefficient due to thickness tolerance. If the chosen steel
plate thickness is 5mm, then 𝐶 = 0.5𝑚𝑚 [19]

So C = 1.5mm

We can calculate the thickness of the vessel wall as S = 0.002334 m = 2.334 mm

Choose S = 5 mm

 Check the stress on the vessel wall based on the test pressure using water:

Because the vessel has a cylindrical welded structure, the pressure inside it is lower than
500,000 N/m2 and higher than 70,000 N/m2. Therefore, the test pressure will be 1.5 times
the internal pressure in the equipment [19]

𝑃 = 1.5 × 𝑃 = 170899.47 N/m2

The stress at the bottom of the equipment under the test pressure is calculated using the
following formula [19]:
[ ( )]×
𝜎= = 4891367.1 N/m2
( )×

We can see that 𝜎 < → The chosen thickness of the vessel wall satisfies the stability
.

condition.

4.2.2.4. Calculation of the diameter of the nozzle

 The nozzle for stream 12

79
For Stream 12 containing both Na-Cellulose solids and solvent liquid → Choose 12 line
pipe inner diameter to be 𝑑 = 100𝑚𝑚.

 The nozzle for stream 11

The diameter of the nozzle will be calculated according to the following formula [19]:

𝑑= (14)
. ×

Where:

V : The flow rate of the flowing solution in the nozzle (m3/s)

w : The appropriate velocity of the solution flowing through the nozzle (m/s)

Volumetric flowrate of stream 11: 𝑉 = = 0.1852 (m3/h) = 5.143×10-5 (m3/s)

Select the veclocity through nozzle to be 0.5 m/s

So, the diameter of the nozzle 11 is 𝑑 = 11.44 (𝑚𝑚)

To comply with the ASME SEC.VII DIV.1, we choose nozzle with size of DN25.

 The nozzle for stream 10

Volumetric flowrate of stream 10: 𝑉 = = 0.5943 (m3/h) = 0.000165 (m3/s)

Select the veclocity through the nozzle to be 0.5 m/s

Applying formula (14) we can calculate the diameter of the nozzle 10 is:

𝑑 = 20.51 (𝑚𝑚)

To comply with the ASME SEC.VII DIV.1, we choose nozzle with size of DN40.

 The nozzle for stream 13

Volumetric flowrate of stream 13: 𝑉 = = 2.941 (m3/h) = 0.000817 (m3/s)

In stream 13, which contains solids, we choose a flow velocity through the nozzle is 0.4
m/s.

Applying formula (14) we can calculate the diameter of the nozzle 13 is:

𝑑 = 51.00 (𝑚𝑚)

80
To To comply with the ASME SEC.VII DIV.1, we choose nozzle with size of DN80.

4.2.2.5. Calculate the bottom thickness of the equipment

We choose an elliptical bottom for the equipment because it is a welded cylindrical body,
vertically oriented, and operates under a pressure greater than 70000 N/m 2

 The bottom and lid thickness of the equipment are calculated using the following
formula [19]
×
𝑆= × +𝐶 (15)
. ×[ ]× ×

Where:

Dt : The inside diameter of the top (lid)/bottom, Dt = 1.9 m

P : Internal pressure of the equipment, P = 113032.98 (N/m 2)

[𝜎] = min([𝜎 ] , [𝜎 ]) = 136.67 (N/m2)

k : The non-integer coefficient depends on the ratio between the diameter of the hole
and the inside diameter of the bottom/lid

𝜑 : Welding joint strength coefficient, 𝜑 = 0.95

ℎ : Height of the bottom/lid of the equipment, ℎ = 0.4 𝑚

C : The thickness allowance coefficient (m)

We have the formula to calculate "k" as follows: [19]

𝑘 =1− (16)

Where:

d : Maximum hole diameter on the bottom/lid of the equipment (m).

The maximum hole diameter on the bottom of the equipment is 𝑑 = 54.76 (𝑚𝑚)

→ 𝑘đ = 0.9712

Because S – C = 5 – 1.5 = 3.5 mm < 10 mm so 𝐶đ will be plus 2 mm → 𝐶đ = 3.5 𝑚𝑚

So, the thickness of the bottom of the equipment is 𝑆đ = 4.2154 𝑚𝑚

We choose 𝑆đ = 5 𝑚𝑚

81
 Check the stress on the vessel wall based on the test pressure using water:

Because the vessel has a cylindrical welded structure, the pressure inside it is lower than
500,000 N/m2 and higher than 70,000 N/m2. Therefore, the test pressure will be 1.5
times the internal pressure in the equipment [19]

𝑃 = 1.5 × 𝑃 = 170899.47 N/m2

The stress at the bottom of the equipment under the test pressure is calculated using the
following formula [19]:

× ×( )×
𝜎= = 146691365.2 N/m2
. × ×( )×

We can see that 𝜎 < → The chosen thickness of the vessel wall satisfies the stability
.

condition.

4.2.2.6. Calculate the lid thickness of the equipment

In this case, we choose an elliptical top (lid) for the equipment because it is a vertically
oriented welded cylindrical body and operates under an internal pressure greater than
70000 N/m2

To calculate the thickness of the lid of the equipment, we still use the two formulas (15)
and (16).

The maximum hole diameter on the lid of the equipment is 𝑑 = 100 (𝑚𝑚)

→ 𝑘đ = 0.9474

Because S – C = 5 – 1.5 = 3.5 mm < 10 mm so 𝐶 will be plus 2 mm → 𝐶 = 3.5 𝑚𝑚

So, the thickness of the lid of the equipment is 𝑆đ = 4.233 𝑚𝑚

We choose 𝑆đ = 5 𝑚𝑚

 Check the stress on the vessel wall based on the test pressure using water:

Because the vessel has a cylindrical welded structure, the pressure inside it is lower than
500,000 N/m2 and higher than 70,000 N/m2. Therefore, the test pressure will be 1.5
times the internal pressure in the equipment [19]

𝑃 = 1.5 × 𝑃 = 170899.47 N/m2

82
The stress at the bottom of the equipment under the test pressure is calculated using the
following formula [19]

× ×( )×
𝜎= = 150378208.1 N/m2
. × ×( )×

We can see that 𝜎 < → C The chosen thickness of the vessel wall satisfies the stability
.

condition.

4.2.2.7. Calculate the steam jacket outer shell of the equipment

We choose the heat transfer medium as saturated steam at 1 bar pressure.

 Saturation temperature of the steam: 𝑇 = 100℃

 Density of saturated steam 𝜌 = 0.763 kg/m3
 Latent heat of condensation of saturated steam 𝑟 = 2256.66 kJ/kg

In the heat balance section, we have calculated the heat energy required to heat the
reaction mass, which is ∆𝑄 = 377547.1 kJ/h

The mass flow rate of steam required to heat the reaction mass is:
∆ ( )
𝑚 = = 184.034 (kg/h)

In which we assume that the heat loss due to the environment accounts for 10%

The volumetric flow rate of saturated steam is:

𝑉 = = 241.198 (m3/h)

Select the steam flow velocity inside the equipment is 𝑣 = 0.2 m/s = 720 m/h

The required annular cross-sectional area for the steam jacket is:

𝐴 = = 0.335 m2

The diameter of the outer steam jacket of the equipment is:

𝐷 = + (𝐷 + 2𝑆) = 2.0186 (m)

Choose 𝐷 = 2.1 𝑚

4.2.2.8. Calculate the impeller design

83
We have:

 The concentration of the solid phase in the feed mixture before the reaction (by
volume) is: 2.2%
 The viscosity of the feed mixture before the reaction is 1.9264× 10 N.s/m2
 The density of the feed mixture before the reaction is 838.867 kg/m 3

→ The two-bladed paddle impeller is chosen because it can create a suspended state for
[18]
fibrous materials with a concentration below 50% . It is suitable for the stirring
environment with a viscosity of μ = 10-3 to 4 N.s/m2 and a density of ρ = 800 to 1900
kg/m3.

We have the ratio:

ℎ 1.6
= = 0.8421
𝐷 1.5

→ Ratio of < 1.4 so the reactor just need only one impeller [20]

The distance between the paddle impeller and the bottom of the equipment is [20]:

ℎ = = 0.533 (m)

Choose ℎ = 0.55 (m)

The diameter of the paddle impeller is [18]:

𝑑 = = 0.633 (m)

Based on the diameter of the two-bladed paddle impeller, we can estimate the rotational
speed n = 7.78 RPS (revolutions per second) [18]

The tip speed of the paddle impeller is:

𝑣 = 𝑛 × 𝜋 × 𝑑 = 15.48 (m/s)

With the two-bladed paddle impeller, the tip speed of the impeller must be within the
range of 1 – 16 m/s [18]. Therefore, a rotational speed of 7.78 RPS is appropriate.

The Reynolds number of the stirred mixture is calculated as follows [18]

𝜌×𝑛×𝑑
𝑅𝑒 = = 1358944.463
𝜇

84
The Froude number of the stirred mixture is calculated as follows [18]

𝑑 ×𝑛
𝐹𝑟 = = 6.2346
𝑔

Since 𝑅𝑒 > 1000, it is necessary to use baffles in the equipment [20]. We will use 2
symmetric baffles.

The height of the baffles is:

ℎ = ℎ − ℎ = 1.2 (m)

The width of the baffles is: [18]

𝑊 = = 0.1188 (m)

Choose 𝑊 = 0.12 m

The mixing coefficient is calculated using the formula [18]

𝑘 = 𝐴 × 𝑅𝑒 × 𝐹𝑟

Where:

A, m, and p are constants determined experimentally [18]

 With the two-bladed paddle impeller, A = 0.985

 With 𝑅𝑒 > 300, m = 0 and 𝑝 = = -0.2241 (Because the paddle impeller

is of the propeller type, and 𝐷 ⁄𝑑 = 3 so a = 2.1 và b = 18)

So, 𝑘 = 0.6536

The power required for the paddle impeller is:

𝑁 = 𝑘 × 𝜌 × 𝑛 × 𝑑 = 26311.108 (W) = 26.311 (kW)

Transmission efficiency 𝜂 = 0.9

Gearbox efficiency 𝜂 = 0.95

Efficiency due to baffles' drag 𝜂 = 0.9

Therefore, the motor power is:

𝑁 = = 34.1925 (kW)
× ×

85
4.2.2.9. Calculate the stirrer shaft design

The allowable shear stress of stainless steel 316.: [𝜏] = 51.5 × 10

Load fluctuation factor 𝐶 = 1

Stirrer shaft angular velocity:

𝜔 = 2 × 𝜋 × 𝑛 = 48.88 (rad/s)

Torque:
×
𝑀 = = 699.47 (N.m)

The diameter of the stirrer shaft is calculated using the following empirical formula:

𝑑 = 1.71 × [ ]
= 0.0408 (m)

Choose 𝑑 = 0.04 m

4.2.2.10. Calculating the support lug for the equipment

 Calculating the mass of the equipment body

The circumference of the equipment is 𝐿 = 𝜋 × 𝐷 = 5.97 (𝑚)

The area of the equipment is 𝐹 =𝐿 × (𝐻 − 2ℎ ) = 12.24 (m2)

The equipment is made from stainless steel 316, and the density of stainless steel 316 is
𝜌 = 7980 (kg/m3) [22]

The thickness of the equipment body is 0.005m → The outer diameter of the equipment
body is 𝐷 = 𝐷 + 2𝑆 = 1.91 (𝑚)

So, the mass of the equipment body is:

×( )
𝐺 =𝜌 ×𝑉 = × (𝐻 − 2ℎ ) × 𝜌 = 489.52 (kg)
 Calculating the mass of bottom and lid of the equipment

The bottom and lid of the equipment have a height of 0.4m and an inner diameter of
1.9m. Referring to Table XIII.10 in document [19], we obtain the inner surface area of
the bottom/lid as 𝐹đ = 𝐹 = 4.16 m2

The thickness of the bottom/lid is 0.005m

86
The mass of the bottom/lid of the equipment is:

𝐺đ = 𝐺 = 𝜌 × 𝐹đ × 𝑆đ = 165.98 (kg)
The total mass of the reaction vessel's lid and bottom is:

𝐺đ + 𝐺 = 2 × 165.98 = 331.97 (kg)

 The mass of the flange, impeller, piping, outer cladding layer, bolts, and heat
transfer material is chosen to be equal to the total mass of the equipment body, lid,
and bottom:

𝐺 = 𝐺đ + 𝐺 = 812.49 (kg)

 Mass of the raw materials introduced into the reaction equipment:

𝐺 =𝐺 +𝐺 +𝐺 = 2362.44 (kg)

 The total mass of the entire equipment is:

𝐺 =𝐺 + 𝐺 + 𝐺 + 𝐺đ + 𝐺 = 4005.42 (kg)

 The gravity load of the entire equipment is:

𝑃 =𝐺 × 9.81 = 39293.16 (N)

Selecting 4 support lugs for the reaction equipment, each support lug must bear a load
of:

𝑃 = = 9823.29 (N)

Select a vertically support lug, refer to table XIII.36 in document [19] to obtain the
parameters:

Table 4.20. Parameters of the support lugs

Allowable gravity load on L B B1 H S l a d

one hanger (N) mm
1.0× 10 110 85 90 170 8 45 15 23

4.3. GENERAL ARRANGEMENT DRAWING FOR ETHERIFICATION

REACTOR
(View in the APPENDIX 2)

87
 CONCLUSIONS
The completed project has achieved the following objectives:

1. Conducted an overview study of Na-CMC product

2. Performed experimental research and established specific technological conditions
for production, including:
 NaOH concentration: 50%w/v
 Molar ratio MCA/AGU: 1.3 (mol/mol)
 Molar ratio NaOH/MCA: 3 (mol/mol)
 EtOH concentration: 80%v/v
 Washing time: 5 times
 Washing volume/time: 20 times the weight of cotton mass

The Na-CMC product synthesized following the project's technology met the quality
standards of the European Pharmacopoeia 2005.

3. Developed a production process for Na-CMC at a capacity of 1000 tons per year,
including material balancing, heat balancing, and design calculations for the
reaction equipment..

88
 REFERENCE

1. Hsieh, Y. L. - Chemical structure and properties of cotton. Cotton, (2007) pp.3–

34. https://doi.org/10.1533/9781845692483.1.3
2. Do, M.H., Van Thi Khuat, K., Huynh, P.T. et al - Synthesis, characterization, and
antibacterial activity of amino-functionalized microcrystalline cellulose
derivatives from cotton fibers. Biomass Conv. Bioref, (2022).
https://doi.org/10.1007/s13399-022-02391-7
3. Cheng, H. N., Dowd, M. K., Selling, G. W., & Biswas, A. - Synthesis of cellulose
acetate from cotton byproducts. Carbohydrate Polymers, 80(2) (2010) pp.449–
452. https://doi.org/10.1016/j.carbpol.2009.11.048
4. Ding, C.; Zhu, X.; Ma, X.; Yang, H. - Synthesis and Performance of a Novel Cotton
Linter Based Cellulose Derivatives Dispersant for Coal–Water Slurries. Polymers,
14 (2022) p.1103. https://doi.org/10.3390/polym14061103
5. Raymond C Rowe, Paul J Sheskey, Siân C Owen – Handbook of Pharmaceutical
Excipients (5th edition), Pharmaceutical Press, London, 2005.
6. Knauft, David A. - Cotton: Origin, History, Technology, and Production. NACTA
Journal, 47(1) (Mar 2003) p.77.
7. Diana Ciolacu, Valentin I. Popa - Structural changes of cellulose determined by
dissolution in aqueous alkali solution. Cellulose Chemistry and Technology, 39(3-
4) (2005) pp.179-188.
8. Shui, T., Feng, S., Chen, G., Li, A., Yuan, Z., Shui, H., … Xu, C.. - Synthesis of
sodium carboxymethyl cellulose using bleached crude cellulose fractionated from
cornstalk. Biomass and Bioenergy, 105 (2017) pp.51–58.
http://doi.org/10.1016/j.biombioe.2017.06.016
9. Panchan, N., Wattanapan, P., Sungsinchai, S., Roddecha, S., Dittanet, P., Seubsai,
A., Niamnuy, C., and Devahastin, S. - Optimization of synthesis conditions for
carboxymethyl cellulose from pineapple leaf waste using microwave-assisted
heating and its application as a food thickener. BioResources 16(4) (2021)
pp.7684-7701.
10. Jia, Fang; Liu, Hong-jie; Zhang, Guo-gang - Preparation of Carboxymethyl
Cellulose from Corncob. Procedia Environmental Sciences, 31 (2016) pp.98-102.
https://doi.org/10.1016/j.proenv.2016.02.013

89
11. Nuran Celikçi, Cengiz Ayhan Ziba and Mustafa Dolaz - Synthesis and
characterization of carboxymethyl cellulose (CMC) from different waste sources
containing cellulose and investigation of its use in the construction industry.
Cellulose chemistry and technology, 56(1-2) (2021) pp.55-68.
https://doi.org/10.35812/CelluloseChemTechnol.2022.56.05
12. Thi Dieu Phuong Nguyen, Nhu Thi Le, Tien Manh Vu, Truong Sinh Pham, Thi
Dao Phan, Ngoc Lan Pham, Thi Tuyet Mai Phan - Synthesis and characterization
of carboxymethyl cellulose with high degree substitution from Vietnamese
pineapple leaf waste. Vietnam Journal of Science, Technology and Engineering,
64(3) (2022) pp.13-18. https://doi.org/10.31276/VJSTE.64(3).13-18
13. ASTM International - ASTM D1439-22 – Standard Test Methods for Sodium
Carboxymethylcellulose. ASTM International (2022).
https://doi.org/10.1520/D1439-22
14. Japanese Pharmacopoeia and Japanese Industrial Standard - JIS K8371 (6th
edition), Japanese Standards Association (JSA), Japan, 2015.
15. Reyes Forsberg, Diana Carolina - Experimental study of alkalinisation of cellulose
in industrial relevant conditions, PhD dissertation, Umeå universitet (2018).
Retrieved from http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-153412
16. N. F. Sayakulu and S. Soloi - The Effect of Sodium Hydroxide (NaOH)
Concentration on Oil Palm Empty Fruit Bunch (OPEFB) Cellulose Yield. Journal
of Physics: Conference Series, 2314 (2022). https://doi.org/10.1088/1742-
6596/2314/1/012017
17. Van Hoof, V., Van den Abeele, L., Buekenhoudt, A., Dotremont, C., & Leysen, R.
- Economic comparison between azeotropic distillation and different hybrid
systems combining distillation with pervaporation for the dehydration of
isopropanol. Separation and Purification Technology, 37(1) (2004) pp.33–
49. http://doi.org/10.1016/j.seppur.2003.08.003
18. Nguyễn Bin, Đỗ Văn Đài, Long Thanh Hùng, Đinh Văn Huỳnh, Nguyễn Trọng
Khuông, Phan Văn Thơm, Phạm Xuân Toản, Trần Xoa – Sổ tay quá trình và thiết
bị công nghệ hóa chất tập 1 (2nd edited). Hanoi Science and Technology Publishing
House, Ha Noi, 1992.

90
19. Nguyễn Bin, Đỗ Văn Đài, Long Thanh Hùng, Đinh Văn Huỳnh, Nguyễn Trọng
Khuông, Phan Văn Thơm, Phạm Xuân Toản, Trần Xoa – Sổ tay quá trình và thiết
bị công nghệ hóa chất tập 2 (2nd edited). Hanoi Science and Technology
Publishing House, Ha Noi, 1992.
20. R. H. Perry - Perry’s Chemical Engineers’ Handbook (7th edition). McGraw-Hill,
New York, 1997.
21. Wapstra, A. H., & Audi, G. - The 1983 atomic mass evaluation. Nuclear Physics
A, 432(1) (1985) pp.1–54. http://doi.org/10.1016/0375-9474(85)90283-0
22. Standard Specification for Chromium and Chromium-Nickel Stainless Steel Plate,
Sheet, and Strip for Pressure Vessels and for General Applications. ASTM, 01.03
(2011) pp.1-13. http://doi.org/10.1520/A0240_A0240M-11
23. Hazardous substance fact sheet: Cotton dust (raw). New Jersey Department of
Health and Senior Services, USA, 2001.
24. Safety data sheet: Sodium hydroxide 99% (version 5.0). Sicherheit, Germany,
2020.
25. Chemical safety sheet: Chloroacetic acid (9th edition). Sigma-Aldrich, EU, 2021.
26. Chemical safety sheet: Iso-Propylol (version 4.1.1.1). Sasol Chemicals, South
Africa, 2016.
27. Chemical safety sheet: Acetic acid. Suong mai trading co., ltd, Vietnam, 2012.
28. Chemical safety sheet: Ethanol. Global Grand Service Trading Company Limited,
Vietnam, 2014.

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 APPENDIX 1

OCCUPATIONAL HEALTH AND SAFETY AND ENVIRONMENT

1. PURPOSES

The human factor is the most important. In labor, humans create material wealth and
invent production tools that promote social development.

Therefore, in production labor, regardless of the circumstances or environment, the

safety and health of the workers must be ensured. For specialized industries such as
chemical technology, workers are exposed to various labor conditions, including
hazardous and harmful factors that may pose risks of occupational diseases.

Thus, ensuring occupational safety is of utmost importance. Consequently, every year,

training and examination on occupational safety must be organized for all employees,
especially those directly involved in production.

2. TOXICITY OF THE RAW MATERIALS

2.1. Cotton [23]
 Symptoms of disease
 Contact with eyes: Cotton dust can cause irritation and damage to the eyes if
in direct contact.
 Inhalation: It can cause bronchoconstriction, chronic bronchitis, and
progressive lung function decline, especially in individuals susceptible to its
effects. Prolonged exposure to cotton dust has been associated with
byssinosis, also known as "brown lung disease”.
 Prevention method
 Use personal protective equipment: When working with cotton dust, wear a
mask, safety goggles, and gloves to protect your eyes, respiratory system, and
skin.
 Adjust the work environment: Ensure good ventilation to reduce exposure to
cotton dust and prevent inhaling it.
 Seek medical attention for symptoms: If you experience discomfort or
irritation after exposure to cotton dust, visit a doctor for appropriate advice
and treatment.
 Storage

92
 Store in a tightly sealed and dry packaging: Keep cotton in a sealed package to
prevent water and moisture exposure, avoiding mold and damage to the cotton's
quality.
 Avoid contact with oil and chemicals: To maintain clean and easy-to-use cotton,
avoid direct contact with oils, greases, and other chemicals.
 Keep away from direct sunlight: Direct sunlight can cause discoloration and
damage to the cotton.
2.2. Sodium hydroxide (NaOH) [24]
 Toxicity
 Acute toxicity
 If swallowed, it can cause severe burns, perforation of the esophagus, and
stomach
 Symptoms: mucous membrane burns, coughing, difficulty breathing,
respiratory damage
 Skin contact: corrosion, skin irritation; severe eye damage. t
 Treatment procedures:
 In case of eye contact: Immediately rinse with water for several minutes and
seek medical attention at the nearest healthcare facility.
 In case of skin contact: Remove contaminated clothing and wash the skin
thoroughly with soap and water. If skin irritation occurs, seek medical
attention at the nearest healthcare facility for evaluation.
 If inhaled: Move to a well-ventilated area and seek medical attention at the
nearest healthcare facility if experiencing difficulty breathing.
 Storage:
 Keep away from water and humid air; store away from areas containing
strong oxidizing agents and easily combustible substances.
 Store in a tightly sealed container to maintain its normal properties, as it can
absorb water from the atmosphere.
2.3. Monochloroacetic Acid (MCA) [25]
 Toxicity:
 It is a highly hazardous substance, with acute toxicity.
 It can cause poisoning when swallowed, contacted with the skin, or inhaled.

93
  It can cause severe skin burns and eye damage.
 It may cause respiratory irritation.
 It is highly toxic to aquatic organisms.
 Treatment procedures
 If it comes in contact with the skin or hair: Immediately remove all
contaminated clothing. Rinse the skin thoroughly with water.
 If inhaled: Move the victim to a well-ventilated and comfortable area to
breathe. Quickly call the poison control center or seek medical advice.
 If it gets in the eyes: Carefully rinse with water for at least 15 minutes and
seek immediate medical attention if experiencing irritation or worsening
symptoms.
 If swallowed: Drink water (up to 2 cups) and seek immediate medical
attention at the nearest healthcare facility. Do not attempt to neutralize with
other chemicals.
 Storage
 Keep Monochloroacetic acid in a cool, dry, and well-ventilated area away
from direct sunlight and heat sources
 Store it in a tightly closed container made of a compatible material (such as
glass or a chemically resistant plastic) to prevent leaks or spills
 Monochloroacetic acid can be hygroscopic, meaning it can absorb moisture
from the atmosphere. To prevent its degradation, store it away from water
sources and humidity.
 Keep Monochloroacetic acid away from strong oxidizing agents, bases, and
other incompatible chemicals to prevent potential hazardous reactions.
 Avoid extreme temperatures, both high and low, as they may affect the
stability of the chemical.
2.4. Isopropanol (IPA) [26]
 Toxicity
 Inhaling the vapors may cause dizziness and drowsiness. These symptoms
can be accompanied by confusion, decreased alertness, loss of reflexes,
impaired coordination, and imbalance.

94
  If swallowed, it can cause headaches, dizziness, fatigue, muscle weakness,
drowsiness, debilitation, unconsciousness, blood vessel rupture, and
behavioral changes. Symptoms like nausea and vomiting can also occur, and
damage to the liver and kidneys may also result.
 It may cause allergies upon skin contact.
 This substance can cause eye irritation and eye damage in some individuals.
 Treatment procedures
 If there is eye contact: Keep the eyes open and rinse thoroughly with running
water. If eye discomfort persists, seek medical treatment.
 If there is skin contact: Immediately remove all clothing and shoes
contaminated with the chemical. Wash the affected areas thoroughly with
water or soap if available. If there is swelling or irritation, seek medical
attention.
 If there is respiratory exposure: Move to an area with fresh air and, if
necessary, use oxygen or perform CPR. Transfer the victim to the nearest
healthcare facility.
 If swallowed: Do not induce vomiting. If vomiting occurs, position the
patient with their head facing forward to maintain the airway. Offer water or
milk to the conscious patient and have them drink slowly. If the patient is
unconscious, do not provide any fluids and promptly take them to a
healthcare facility.
 Storage
 Do not use aluminum or plated containers; instead, use high-density plastic
or glass containers.
 Avoid close contact with strong oxidizing agents and strong acid-base
substances
 Isopropanol can absorb moisture from the air, which may reduce its
effectiveness. Keep the container tightly closed when not in use to prevent
exposure to moisture.
 Isopropanol is flammable. Keep it away from open flames, sparks, and
sources of ignition. Do not smoke or use electrical equipment that may cause
sparks near the storage area.

95
  Avoid extreme temperatures. The ideal storage temperature for isopropanol
is between 15°C to 30°C
2.5. Acid acetic [27]
 Toxicity
 Extremely hazardous upon contact with the skin and eyes (causing irritation),
ingestion, or inhalation.
 Toxic when in contact with the skin and eyes (corrosive).
 Liquid or mist can cause tissue damage, especially to the eyes, mouth, and
respiratory tract.
 Skin contact can cause burns, skin inflammation, and dry cracked skin.
 Inhalation of vapors can lead to severe respiratory irritation, possible central
nervous system (CNS) depression resulting in dizziness, lightheadedness,
headaches, and nausea. Other signs and symptoms of CNS depression may
include headaches, nausea, and loss of motor control. Continued inhalation
may lead to unconsciousness and death.
 Treatment procedures
 In case of eye contact: Carefully flush the eyes with clean water for at least
15 minutes while keeping the eyelids open. Transfer the victim to the nearest
healthcare facility for further care.
 If there is skin contact: Immediately remove the contaminated clothing. Rinse
the affected area with clean water (and soap if possible).
 If there is respiratory exposure: Move the victim to a well-ventilated area. If
there is no rapid improvement, take the victim to the nearest healthcare
facility for further treatment. Keep the victim's chest in a position favorable
for breathing.
 If swallowed: Immediately call the emergency center or a doctor. Do not
induce vomiting. If the victim vomits, keep the head lower than the hips to
prevent aspiration.
 Storage
 Store acetic acid in a tightly sealed container made of a compatible material,
such as glass or HDPE plastic, to prevent leaks or spills

96
  Keep the container in a cool, dry, and well-ventilated area. Avoid direct
sunlight and heat sources
 Keep acetic acid away from incompatible substances, such as strong
oxidizing agents and bases, to prevent hazardous reactions.
 Acetic acid is flammable. Keep it away from open flames, sparks, and
sources of ignition. Do not smoke or use electrical equipment that may cause
sparks near the storage area.
2.6. Ethanol (EtOH) [28]
 Toxicity
 Eye exposure: Signs and symptoms of eye irritation may include a burning
sensation, redness, swelling, and/or blurred vision.
 Respiratory exposure: Inhaling high concentrations of the substance can lead
to central nervous system (CNS) depression resulting in dizziness,
lightheadedness, headaches, and nausea. Other signs and symptoms of CNS
depression may include headaches, nausea, and loss of motor control.
Continued inhalation may lead to unconsciousness and death.
 Skin exposure: Signs of skin inflammation and symptoms may include a
burning sensation and/or dry/cracked skin.
 Gastrointestinal exposure: If the material enters the lungs, signs and
symptoms may include cough, shortness of breath, wheezing, difficulty
breathing, chest tightness, choking, and/or fever.
 Liver damage may manifest through loss of appetite, jaundice (yellowing of
the skin and eyes), fatigue, bleeding or bruising easily, occasional abdominal
pain, and swelling in the upper abdomen.
 Treatment procedures
 In case of eye contact: Carefully flush the eyes with clean water for at least
30 minutes while keeping the eyelids open. Transfer the victim to the nearest
healthcare facility for further care.
 If there is skin contact: Immediately remove the contaminated clothing. Soak
the skin in clean water for at least 15 minutes, then wash with soap if possible.
If the skin becomes red, swollen, painful, and/or blistered, transfer the patient
to the nearest healthcare facility for further treatment.

97
  If there is respiratory exposure: Move the victim to a well-ventilated area. If
there is no rapid improvement, take the victim to the nearest healthcare
facility for further treatment. Keep the victim's chest in a position favorable
for breathing.
 If swallowed: Immediately call the emergency center or a doctor. Do not
induce vomiting. If the victim vomits, keep the head lower than the hips to
prevent aspiration
 Storage
 It must be stored in a well-ventilated area, away from sunlight, sources of
ignition, and other heat sources.
 Keep away from sprays, flammable substances, oxidizing agents, corrosive
materials, and other easily combustible products that are harmful to humans
or the environment.
 Vapors in the container should not be allowed to escape into the air. Breathing
should be controlled with an appropriate vapor control system.
 Maintain the chemical container's temperature in line with the surrounding
environment.
 Close the storage container tightly when not in use. Do not use compressed
air for filling, discharging, or handling.
3. OCCUPATIONAL SAFETY AND HEALTH
3.1. Fire prevention and fighting requirements
 Prohibit the use of open flames, firewood, cooking, and smoking in production
warehouses and areas where fire is not allowed.
 Organize supplies and goods in a neat and clean manner, separating them by type
and maintaining a safe distance to prevent fires. Keep them away from the roof
and walls for easy inspection and rescue if needed.
 Have fire-fighting equipment readily available and easily accessible, reserved
solely for firefighting purposes and not for other uses. Adhere strictly to
operational and technical requirements when using equipment.
 When repairing equipment, ensure that all toxic gases are expelled from the
equipment using inert gas before proceeding with the repairs.

98
 Maintain a well-trained and equipped fire prevention and fighting team ready to
respond to incidents effectively.
 In the event of a fire or explosion, take necessary technical measures to prevent
the fire from spreading to adjacent areas, such as halting production, cutting off
power, and activating fire alarms.
3.2. Labor protection equipment
 Clear and specific guidelines should be provided for adhering to labor safety
regulations and implementing technical operations correctly during work.
 Workshops should be equipped with necessary protective gear such as protective
clothing, masks, goggles, boots, and rubber or nitrile gloves to prevent skin
corrosion. Protective equipment, gloves, and rubber boots used when handling
chemicals should be cleaned immediately after use. Prior to operation, equipment
and pipes should be inspected for tightness, dents, signs of wear from rubbing, or
internal corrosion.
 Strictly adhere to technology requirements.
 Thoroughly inspect raw materials before initiating production.
 When operating equipment, handle it gently, with care, and precision.
 Full compliance with electrical safety regulations, avoiding any alterations to
different types of bridges, and ensuring the bridge system solely protects the
equipment within the electrical cabinet.
 Clean machines and equipment after use.
 Regularly monitor workers' health to detect common illnesses early, prevent their
occurrence, and ensure compliance with the State's labor regulations.
4. ENVIRONMENTAL SANITATION
4.1. Handling chemical spills and leaks

Immediate action is crucial when dealing with chemical spills to prevent harm to
personnel and the environment, as these spills can lead to the release of toxic or
flammable fumes. Floors should be constructed with impervious (sealed) concrete or
other non-porous materials, and any contaminated parts should be removed.

For liquid spills:

99
 Apply sawdust, sand, or dry soil to the affected area and allow it to absorb the
chemical for a few minutes.
 Wear protective nitrile rubber gloves and a mask while handling the spill.
 Sweep or scoop up the sawdust, sand, or dry soil containing the absorbed chemical
and place it in a labeled container for proper disposal.
 Clean the spilled area thoroughly using soap or a strong detergent.detergent
4.2. Treatment of emissions and wastewater

Emissions treatment:

 To position hazardous equipment away from densely populated areas and install a
ventilation system to ensure proper airflow, the exhaust gas treatment zone should
be situated at the downwind end.
 Once collected, the exhaust gas undergoes treatment using methods like
absorption, adsorption, neutralization, or suction.

Wastewater treatment:

 Wastewater often contains a variety of chemicals, impurities, and metal salts.

 The treatment of wastewater is divided into three stages:
 Stage 1 treatment: This stage involves pre-treatment and settling processes,
which aim to remove large solid impurities from the wastewater to protect
pumps and pipelines for subsequent treatment technologies.
 Stage 2 treatment: This stage comprises biological and chemical processes
such as biological filtration and oxidation in tanks with no decomposition.
The anaerobic process helps reduce the majority of dissolved organic
substances through biological means.
 Stage 3 treatment: This stage includes microfiltration, chemical precipitation,
coagulation, activated carbon band adsorption, zeolite, cation exchange,
nutrient permeation, chlorination, and ozonation. Conversely, these processes
are effective in reducing substances.
4.3. Technical measures
 Implementing mechanization and automation in the production process to reduce
human exposure to toxic substances.

100
 Upgrading and adopting advanced cleaning methods and technologies, while
ensuring a well-ventilated and well-lit working environment.
 Adopting cleaner and more environmentally friendly technologies to minimize
pollution. Emphasizing industrial hygiene measures.
 Ensuring the sealing of equipment to prevent leaks or spills of hazardous
substances.
 Eliminating potential ignition sources in areas susceptible to fire and explosion.
Installing visible fire warning signs and placing fire extinguishing tools in easily
accessible locations in fire-prone areas.
 In the event of an explosion, implementing necessary technical measures to
prevent the fire from spreading to neighboring areas, such as halting production,
cutting off power, and taking immediate firefighting actions.
 Educating and promoting awareness among workers about safety precautions to
ensure a secure production process.

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 APPENDIX 2

PROCESS DIAGRAM AND EQUIPMENT DESIGN DRAWINGS

Name of drawing Symbol Quantity

Block diagram 2023-CMC-BD-001 01

Process flowing diagram 2023-CMC-PFD-001 01

Process and instrumentation diagram

2023-CMC-P&ID-001 01
drawings

General Arrangement drawings 2023-CMC-GAR05-001 01

102