CHAPTER ONE

1.1HISTORY OF SIWES
The student industrial work experience (SIWES) is a skill training program
designed to expose and prepare students of university, polytechnics/college of
agriculture and colleges of education for the industrial work situation they are
likely to meet after graduation.

The scheme also offers students opportunity of familiarizing with machinery

that is usually not available in their institution. Before the establishment of that
scheme there was a growing concern among our industrialist that the graduate
of our institution of higher learning lacked adequate practical background
studies in preparatory for employment in industries. Thus, the employers were
of the opinion that the theoretical education going on in higher institution was
not responsive to needs of the employers of labor.

It is against this background that the government’s decree No.47 of 8 th Oct;

1971 as amended in 1990, highlighted the capacity building of human resources
in industry, commerce and government through training and retraining in
industry, commerce and government through training and retraining of workers
in order to effectively provide the much needed quality goods and services in a
dynamic economy as ours, led to the establishment of Industrial Training Fund
(ITF) in 1973/1974. It is due to the growing concern among our industrialist that
graduates of our tertiary institutions lack adequate practical background studies
preparatory for employment in industries led to the formation of Students
Industrial Work Experience Scheme (SIWES), by Industrial Training Fund
(ITF), in 1993/1994, to acquaint students with skills of handling employer’s
equipment and machinery. The Industrial Training Fund (ITF) solely funded the
scheme during formative years but as the financial involvement became
unbearable to the fund, it withdrew from the scheme in 1979. Later the Federal
Government in November, 1984 revert the management and implementation of

1
SIWES program to ITF and it was effectively taken over by the Industrial
Training Fund (ITF). With the funding being solely borne by the government,
ITF has one of its key functions; to work as cooperative entity with industries
and commerce where students can undertake mid-career work experience
attachment in industries.

1.1.1 PURPOSE OF REPORT

The industrial attachment program fulfils part of the requirements in pursuing

Bachelor degree of engineering (B.Eng.) in CHEMICAL ENGINEERING, in
NNAMDI AZIKIWE UNIVERSITY AWKA. This report serves to summarize
the activities and experience gained with New Age Pharmaceutical industry
limited, Gwagwalada, Abuja-Nigeria.

1.1.2 AIMS OF SIWES

The institution of SIWES is aimed at bridging the gap existing between

theoretical and practical experience which was missing in the educational
system. It was also aimed at building the students on having peaceful
coexistence with other workers when they graduate.

1.1.3 OBJECTIVES OF SIWES

Specifically, the objectives of the Student Industrial Work Experience Scheme

as among others are:

 Prepare students for the work situation they are likely to meet after
graduation.
 Provide students with the opportunity to apply their theoretical knowledge in
real work situation, thereby bridging the gap between university work and
actual practical.
 Expose students to work method and technique in handling equipment and
machinery that not be available in their institution.

2
 Make the transition from the university to the world of work easier and this
enhances student’s contract for later job placement.
 To provide an avenue for students in the Nigerian university to acquire
industrial skill experience in the course of study.

1.1.4 STAKEHOLDERS IN SIWES

 Federal government, through the ministry of commerce and industry.
 ITF, SIWES division through Industrial Attachment Grants &
Reimbursement department.
 The supervising or regulatory agencies – NUC, NBTE and NCCE (National
Commission for College of Education).
 Employers of labor.
 Tertiary institutions.
 Students.
 National employers* Consultative Associative (NECA).
 National Association of Chambers of Commerce, Industry, Mines and
Agriculture.
 Manufacturer Association of Nigeria.
 NAFDAC, National Agency for Foods, Drugs and Administration Control.

1.2 CORPORATE PROFILE OF NEW AGE PHARMACEUTICAL

INDUSTRY LIMITED

1.2.1 History, Growth and Development:

New Age Pharmaceutical Industry Limited (NAPIL) began as a marketing firm

in the ancient city of kano in 2011 and specialized in the importation and sales
of quality pharmaceutical products. It relocated to Gwagwalada in the Federal
Capital Territory, Abuja in 2013 to begin operations in the production,

3
distribution and sales of quality pharmaceutical products. It began full
operational activities in the year 2014 after due registration and inspection by
relevant regulatory authorities such as the National Agency for Food and Drug
Administration and Control (NAFDAC), Pharmacists Council of Nigeria
(PCN), Corporate Affairs commission (CAC). In order to ensure and maintain
the production of healthy and quality medicines which are circulated in the
market, professionals such as Pharmacists, Chemists, Biochemists,
Microbiologists, Engineers, Technicians and other technician staff were
employed to satisfy her esteemed customers who yearns for safe and quality
medicines. Presently, the company is into the production of only oral liquid
(syrups) and oral solid (tablets) pharmaceutical dosage forms. The industry
adheres strictly to guidelines laid down by both international and indigenous
regulatory bodies such as Current Good Manufacturing Practices (cGMP), Good
Laboratory Practices (GLP), Standard Operating Procedures (SOP) and other
safety rules that will ensure the safety of both personnel’s and products.
Presently, the company has 20 different products both in the oral liquid and oral
solid dosage forms. NAPIL occupies a land mass of about 11 acres situated at
231/234 kuje road Gwagwalada, Abuja.

1.2.2 MANAGEMENT AND STAFF STRENGHT

The administration, business and financial management of the company is under

the control of the managing director. Out of over 300 workers, about forty
percent of the workers are skilled, about forty-five percent are semi-skilled
while about fifteen percent are unskilled. The workers are categorized into head
of department, managers, supervisors, operators and assistants. There are
functional department that are headed by expatriates, they are;

4
 Financial and Administrative Department: this department is charged
with managing the affairs of the company and all the staffs. This department
is headed by the managing director (MD).
 Quality Control Department: this where the quality of productis controlled
to ensure stability and it is made of professional chemist, biochemist,
microbiologist. It is headed by a Q.C manager.
 Quality Assurance Department: this is where the products quality is
assured before it is moved out. They work with the quality control
department and check the results obtained by the Q.C department, make use
of the result and certify the product. This department is headed by a Q.A
manager.
 Pharmacist Department: this department include a group of professional
pharmacist and is headed by one called the superintendent pharmacist.
Everything on drugs formulation is under their control.
 Production Department: this department is in charge of the production and
packaging of the drugs (oral solid/liquid dosage drug). They are headed by
supervisors and they work very closely and under the production pharmacist.
 Cleaning Department: this department is in charge of maintaining an
hygienic work environment. Majorly consist of unskilled workers and
headed by a supervisor.
 Engineering Department: this department is charged with the duty of
maintenance and repair of equipment/machines used in the plant. They are
made of a team of trained and experienced engineers and head by a
supervisor.
 Security Department: this department is in charge of securing the company
environment. This department is headed by a chief security officer (CSO).
 Printing Department: this department is responsible for the printing of
labels and leaves on packaging materials. They are headed by a supervisor.

5
 Packaging Department: this department is responsible for packaging
finished goods immediately they have undergone quality check (under test).
They are headed by supervisors.

1.2.3 POLICIES AND OBJECTIVES OF THE COMPANY

For every company, the major objectives are the acceptance of products by
the free market coupled with maximization. NAPIL is not left out of this,
the other objectives which include production of genuine pharmaceutical
products of acceptable conditions to their customers.
Although the company policies are determined by indigenous bodies such
as the company’s board and national bodies like NAFDAC and PCN. These
policies also come in form of Current Good Manufacturing Practices
(cGMP), Good laboratory Practices (GLP) and Standard Operating
Procedures (SOP). There are seven golden rules that make up the current
good manufacturing practices (cGMP), they are;
1. Get the facility design right from the start; layout the production area to
suit the sequence of production to reduce the chances of cross
contamination and to avoid contamination and errors.
2. Validate processes establishing documented evidence that provides a high
degree of assurance that a specific process will constantly produce a
product meeting its pre-determined specifications and quality attributes.
3. To prove that equipment and processes consistently do what they are
supposed to do, testing and documentations are required.Write good
procedures are followed. In drug manufacturing industry, it is critical that
good procedures are in place to ensure a controlled and consistent
performance; it is an essential part of GMP.
4. Identify who does what; all employees should clearly understand what
they have to do each day. It avoids misunderstandings and minimizes the
risk to product quality.

6
5. Keep good records; Good records enable you to track all activities
performed during batch manufacturing from the receiving of raw
materials to the final product released; they provide the history of the
batch and its distribution. In cGMP if it is not written down, then it did
not happen.
6. Practice good hygiene; it is critical to reduce the risk of product
contamination to a minimum level by putting in place a sanitation
program.
7. Train and develop staff; To meet GMP requirements, it is essential to
have the right people to do the right job.Provide training for all
employees.
I.2.4 SAFETY PRECAUTIONS IN THE COMPANY
II. Nose/Face mask and safety boots were provided to the staff to prevent
contaminant.
III. Fume cupboard were also provided for mixing of fuming chemicals.
IV. Water tap and sinks were also provided in the laboratory for washing
off chemicals especially when spilled on the body.
V. Fire extinguishers and fire exits were at strategic points to prevent fire
hazards in the company
VI. Safety clothes such as laboratory coats and head gear were also
provided for staff in the company for protection.

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 1.2.5 NEW AGE ORGANIZATIONAL CHART

MD/CEO

Generator Marketing Accountant QA Superintendent

Supervisor/ Manager pharmacist
Secretary
CSO

Security QC
Officers Manager

Productio Productio
n Senior QA n
Chemica
IPQA Mainte Pharmacis
Pharmacis Docume l Raw
OFFICER( nance QC Asst t Tablet
t Syrup ntation Material
SYRUP) Che .QC
Supr. officer MGT
Printing mist Che
Officer
Maintenance mist
Supr. PET Bottles Process Superviso
Washers Supervisor r
IPQA Packaging Senior
Maintenan Officer MGT Dispensin
ce officer (Tablet Officer g Officer Fin. Goods
W/H Asst.
Day/Nigh
Day/Night Tablet
Manager Super
t Mach. Mach.in
Workers Cleaning visor
Oper. The
Asst.Dis Oper. Supervisor
Supr.Printing
pensing ISupr.II
Officer
Utility
LOADERS
maintenace MACHINE OPERATORS PACKA
Officer
GERS
(TABLET&SYRUP)
CLEANERS

CHAPTER TWO

8
 REVIEW OF RELATED LITERATURE

2.1 PHARMARCEUTICAL CHEMICALS

Pharmacologically active substances may be categorized as natural
products and synthetic drugs. Natural products are derived from plant and
animal sources, while synthetic drugs are produced by microbiological and
chemical technologies. Antibiotics, steroid and peptide hormones, vitamins,
enzymes, prostaglandins and pheromones are important natural products.
Scientific research is focusing increasingly on synthetic drugs due to recent
scientific advances in molecular biology, biochemistry, pharmacology and
computer technology.
Organic and inorganic chemicals are raw materials, serving as reactants,
reagents, catalysts and solvents. The Industrial chemicals are used in
researching and developing active drug substances (API) and manufacturing
bulk substances (EXCIPENTS) and finished pharmaceutical products. The use
of industrial chemicals is determined by the specific manufacturing process and
operations. Many of these materials may be hazardous to workers. Since worker
exposures to industrial chemicals may be hazardous, occupational exposure
limits, such as threshold limit values (TLVs) have been established by
government, technical and professional organizations (Naumann et al. 1996;
Sargent and Kirk 1988). Active drug substances and exicipents materials are
combined during pharmaceutical manufacturing to produce dosage forms of
medicinal products (e.g., tablets, capsules, liquids, powders, creams and
ointments) (Gennaro 1990). These section would be discussed under the
following sub heading:
 Manufacturing process(process And production of drug)
 Laboratory process

2.1.1 MANUFACTURING PROCESSES FOR SOLID/TABLET ORAL

DOSAGE:

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Pharmaceutical manufacturing process may be categorized as basic production
of bulk drug substances and pharmaceutical manufacturing of dosage form
products.The manufacturing steps begin with the assembly and pre-weighing of
both active ingredients and excipients (inactive ingredients) in an isolated room
under local exhaust ventilation. the ingredients are moved to a granulation
room. The active ingredients and excipents are milled. The initial blending of
the ingredients is done in a wet state. At the end of the wet blending process, the
granulation is typically moved to a wet mill, where particles in the mix are
reduced to a specific size. The milled granulation is then dried using a fluid bed
drier. The dried granulation may or may not undergo the addition of a lubricant
before dry-blending and/or dry-milling, depending on the specific product and
process. The final granulation, ready to be made into tablets, is then stored in
sealed containers. The raw materials and granulation, and sometimes the
intermediate products, are typically sampled and assayed by quality-control
personnel prior to being moved to the next process step. When needed, the
granulation is moved to a compression room, where it is made into tablets by
means of a tablet press. Formed tablets exit from the machine through tubing at
the side, and drop into plastic-lined drums. When filled, the drums are sampled
and inspected. After assay by quality-control personnel, the drums are sealed,
stored and staged for packaging operations. Some tablets also undergo a coating
process, in which layers of edible wax and sometimes sugars are used to seal the
tablet.
The tablets are packaged by sealing them in blister packs or bottled,
depending on the nature of the product. In this process, the containers of tablets
are moved to the packaging area. The tablets may be manually scooped into the
packaging machine hopper or fed by means of a vacuum wand. The tablets are
then either immediately sealed between layers of aluminium foil and plastic
film (blister-packaging) or they are bottled. The blister packs or bottles are then

10
conveyed along a line on which they are inspected and placed in pouches or
boxed with appropriate inserts.

2.1.1.1. OPERATING PROCESS

1. RECEIVING BAY:

This is the unit where raw materials are received in good conditions.

2. SAMPLING BROTH:

This is where received raw materials are analyzed and tested.

3. RAW MATERIAL QUARANTINE ROOM:

This is the unit where received raw materials undergoing test are kept.

4. APPROVED RAW MATERIAL ROOM:

Raw materials that have being analyzed and has passed its test are kept in this
unit.

5. DISPENSING ROOM:

The quantity of raw materials to be used for production is weighed in this room.
Weighing and dispensing. Weighing and dispensing of solids and liquids is a
very common activity throughout the pharmaceutical industry (Gennaro 1990).
Usually workers dispense materials by hand-scooping solids and pouring or
pumping liquids. Weighing and dispensing are often performed in a warehouse
during bulk chemical production or in a pharmacy during pharmaceutical
dosage-form manufacturing. Due to the likelihood of spills, leaks and fugitive
emissions during weighing and dispensing, proper workplace control measures
are necessary to protect workers. Weighing and dispensing should be performed
in a partitioned workplace area with good dilution ventilation. The work
surfaces in areas where materials are weighed and dispensed should be smooth
and sealed, permitting their proper cleaning. LEV with backdraft or sidedraft

11
hoods prevents the release of air contaminants when weighing and dispensing
dusty solids or volatile liquids (Cole 1990). Weighing and dispensing highly
toxic materials may require additional control measures such as laminar
ventilation hoods or isolation devices (e.g., glove boxes or glove bags)
(Naumann et al. 1996).

8. GRANULATION HALL:

Granulators have different designs and features with varying containment and
control of mechanical hazards and airborne dusts and vapours (Perry 1984;
Swarbick and Boylan 1996). Enclosed granulators can be vented to air-control
devices, reducing emissions of solvent vapours or dusts to the workplace.
Eyewashes and safety showers are needed, if workers accidentally contact
solvents or irritating dusts. Involves the follow steps
1. MASS MIXER:the mass mixer is designed for uniformly mixing of dry and
wet material and especially suitable for powder of Pharmaceuticals, Food,
Herbal, Agro Chemicals & Chemicals. Specially designed self-adjusting
sealing arrangement of unique design is provided to ensure that no black
particle enters into the mixing drum. The material under mixing process can
be monitoring through acrylic dust cover and its controls dusting and
contaminations. The tilting device is provided to make easy the unloading of
the material and easy cleaning of the mixing drum.

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 FIG1: MASS MIXER

2. MILLERS: dry solids are milled to change their particle characteristics

and produce free-flowing powders. Mills have different designs and
features with varying containment and control of mechanical hazards and
airborne dusts (Kroschwitz 1992; Perry 1984). Prior to milling materials,
their physical properties and hazards should be reviewed or tested.
Explosion prevention and protection measures involve installing dust-
tight electrical equipment and utilities, grounding and bonding equipment
and accessories to eliminate electrostatic sparking, installing safety relief
valves on enclosed mills, and constructing blast relief panels in walls.
These measures may be necessary due to the explosivity of some drug
substances and excipients, high dust levels and energies associated with
milling operations. Water- or solvent-wet solids are dried during many
pharmaceutical manufacturing operations. the active ingredients and
excipients are wetted with aqueous or solvent solutions(binder) to
produce course granules with enlarged particle sizes.

13
 FIG2: DIAGRAM OF MILLERS

3. DRYER: Dryers have different designs and features with varying

containment and control of vapours and dusts . The granules are dried, we
used fluidized bed driers incorporating a heat pump drying mechanism
have been developed at the Norwegian Institute of Technology (Alves-
Filho and Strømmen, 1996).The drying chamber receives wet material
and discharges dried product through the product inlet and outlet ducts.
The desired operating temperature is obtained by adjusting the condenser
capacity, while the required air humidity is maintained by regulating the
compressor capacity via frequency control of the motor speed. According
to Alves-Filho and Strømmen (1996), this set-up can produce drying
temperatures from –20 to 60°C and air humidity spanning 20 to 90 per
cent. The two-stage system simply comprises two fluidized beds
connected in series. Two heat pumps supply conditioned air
independently to each drying chamber. The drying chambers are
connected in series so that one receives wet product and discharges the
semi-dried product to the next, which produces the final dried product.
The advantages of multiple-stage fluidized bed drying over single
fluidized bed heat pump drying include improved product quality and
enhanced energy efficiency (Alves-Filho and Strømmen, 1996) but at

14
higher capital cost. Recently, Taechapairoj et al. (2003) employed a
fluidized bed system incorporating superheated steam as the drying
medium for paddy drying. They observed that when using superheated
steam drying the head rice yield is more sustainable and has higher values
than those obtained from hot air drying. However, there was some colour
depreciation in terms of the rice whiteness. The main cause of the rapid
change in the colour is partly due to the steam condensation on the paddy
surface. Fluidized bed drying (FBD) has found many applications for
drying granular solids in the food, pharmaceutical and agriculture
industries. For drying of powders in the 50–2000 µm range, FBD
competes successfully with other more traditional drier types, e.g. rotary,
tunnel, conveyor, continuous tray, etc.

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FIG 3: DIAGRAM OF FLUID BED DRYER

9. COMPRESSION ROOM:

This is where Slugging or dry granulation blends and compresses relatively

large tablets which are ground and screened to a desired mesh size, then
recompressed into the final tablet compressed into different shapes/sizes by the
compression machine, a metal die holds a measured amount of the drug blend
while a punch compresses the tablet. Blended and granulated materials may also
be produced in capsule form. Hard gelatin capsules are dried, trimmed, filled
and joined on capsule-filling machines. Compression equipment has different
designs and features with varying containment and control of mechanical
hazards and airborne dusts (Gennaro 1990; Swarbick and Boylan 1996).
Compression equipment may pose serious mechanical hazards if inadequately

16
guarded. High noise levels may also be produced by compression and slugging
operations.

FIG4: DIAGRAM OF COMPRESSOR

10. COATING ROOM:

This is the unit where some medicines that are harmful to the stomach without
coating are coated to mask the taste and odor of the tablet.

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FIG5: DIAGRAM OF COATING MACHINE

11. BLISTERING ROOM:

This is the unit where tablets are blistered. The tablets are packaged by sealing
them in blister packs or bottled, depending on the nature of the product. In this
process, the containers of tablets are moved to the packaging area. The tablets
may be manually scooped into the packaging machine hopper or fed by means
of a vacuum wand. The tablets are then either immediately sealed between
layers of aluminium foil and plastic film (blister-packaging) or they are bottled.
The blister packs or bottles are then conveyed along a line on which they are
inspected and placed in pouches or boxed with appropriate inserts.

18
FIG 6: DIAGRAM OF BLISTERING MACHINE

12 .PACKAGING HALL:

This is where finished products are packaged for distribution. Pharmaceutical

packaging operations are performed with a series of integrated machines and
repetitive manual tasks (Gennaro 1990; Swarbick and Boylan 1996). Finished
dosage-form products may be packaged in many different types of containers
(e.g., plastic or glass bottles, foil blister packs, pouches or sachets, tubes and
sterile vials). The mechanical equipment fills, caps, labels, cartons and packs
the finished products in shipping containers.

13. SHRINK WRAPPING ROOM:

Packaged products are being shrink wrapped in this unit and are taken to the
finished product warehouse where it will be conveyed to desired locations.

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FIG7: DIAGRAM OF SHRINK WRAPPING MACHINE

2.1.2. LABORATORY OPERATIONS

Laboratory operations in the pharmaceutical industry are diverse. They may

pose biological, chemical and physical hazards, depending upon the specific
agents, operations, equipment and work practices employed. Major distinctions
exist between labs which conduct scientific research and product and process
development and those which evaluate quality assurance and control activities
(Swarbick and Boylan 1996). Lab workers may conduct scientific research to
discover drug substances, develop manufacturing processes for bulk chemical
and dosage-form products or analyze raw materials, intermediates and finished
products. Lab activities should be evaluated individually, although good lab
practices apply to many situations (National Research Council 1981). Clearly
defined responsibilities, training and information, safe work practices and
control measures and emergency response plans are important means for
effectively managing environmental, health and safety hazards.Biological safety
hoods provide downward and inward laminar flow, preventing the release of
micro-organisms (Gennaro 1990; Swarbick and Boylan 1996)..

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2.1.2.1. EQUIPMENTS IN THE LABORATORY

1. pH METER: Used to measure hydrogen ion concentration. In other

words, it gives the degree of acidity or alkalinity of a substance

Fig 8: Diagram of pH meter

2. TITRATION APPARATUS: This is used to determine the
concentration of substance in a solution. It involves introducing a solution
of known concentration (titrant) into another whose concentration is to be
determined (analyte). A point is reached (end-point) when the titrant
would have displaced an equal volume of the substance whose
concentration is yet to be determined. To note the end-point, a suitable
indicator which responds to colour change depending on the pH of the
analyte and the titrantis employed.

Fig 9: Diagram of titration apparatus

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3. CONDUCTIVITY METER: Used as an indicator of the amount of
dissolved substances in a solution, and also to determine the conductivity
of water.

Fig 10: Diagram of Conductivity Meter

4. SPECTROPHOTOMETER: Used to measure the amount of light of a
specific wavelength which passes through a medium. it operates based on
the principle of Beer and Lambert’s law

Fig 11: Diagram of Spectrophotometer

5. WEIGHING BALANCE: Used to measure weight or calculate mass.

Fig 12: Diagram of Weighting Balance

22
6. FRIABILITY TESTER: Used to test the durability of medicines during
transit or when agitated.

Fig 13: Diagram of Friability Tester

7. VENEIR CALIPER: Used to measure the diameter of tablets.

Fig 14: Diagram of Venier Caliper

8. DISSOLUTION TESTER: This is used to determine the amount of the
active ingredient of a tablet that will be absorbed in the body after a
particular time. It is also known as the bioavailability of the active
pharmaceutical ingredients in the body which can elicit a therapeutic
effect

23
 Fig 15: Diagram of Dissolution Tester
9. DRUG HARDNER TESTER: This is used to test the hardness of
tablets.

Fig 16: Diagram of Hardner Tester

10.CENTRIFUGE MACHINE: Used for separation of fluids, gas, or

liquid, based on density.

24
 Fig 17: Diagram of Centrifuge Machine
11.DESSICATOR: This is a sealable enclosure containing desiccant such as
silica gel used for preserving moisture-sensitive substances.

Fig 18: Diagram of Dessicator

12.VISCOMETER: Used to measure the viscosity (thick, sticky) of a fluid.

Fig 19: Diagram of Viscometer

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13.WATER BATH: This is laboratory equipment made from a container
filled with heated water. It is used to incubate samples in water at
constant temperature over a long period of time. It is also used for
indirect heating or heating flammable substances. The temperature of the
water bath can be adjusted to suit a particular need.

Fig 20: Diagram of Water Bath

14.FUME CUPBOARD: This is a closet that is designed to limit exposure
to hazardous or toxic fumes, vapors or dust. It protects the user from
inhaling toxic gases; it protects the environment, and also protects the
product or experiment.

Fig 21: Diagram of Fume Cupboard

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 15. LABORATORY GLASS WARES: these are equipment made of
glasses and they include; conical flask, volumetric flask, density bottle,
pipette, beaker etc.

Fig 22: Diagram of Glass Wares

2.1.2.2 WATER TREATMENT AND WATER ANALYSIS

Water Treatment?

Is any process that improves the quanlity of water to make it appropriate for a
specific end use. The end use can be for drinking, industrial water
supply,irrigation etc including being safely returned to the
environment.pharmaceutical company must employ a range of treatment and
monitoring processes to ensure the impurities present in water do not interfere
with its intended use. The chemical and biological impurities present in water
are continually changing which have led to the complexity of water chemistry.
There are two kinds of water treatment common to pharmaceutical industries
(NAPIL,2021). They include:

1. Chemical process or chlorination and dechlorination

2. Physical process or passing the water through filters; coarse sand filter,
fine sand filter, activated carbon filter, resin filter, micro filters and UV
sterilizer.

1a. CHLORINATION:is a process of adding chlorine or chlorine

compounds such as sodium hypochlorite to water to make it safe for use.

27
This method is used to reduced bacteria, viruses and microbes in water (this
helps to prevent water borne diseases) by a minimum of 70%.

1b.DECHLORINATION: is a process of removing residual chlorine from

disinfected water prior to discharge for use.

2a. COARSE SAND FILTER: it ranges from 50 microns to 200 microns

and is used to remove suspended large solids from disinfected water. In
order to prevent breakdown of filter, we carry out backwashing.

2b. FINE SAND FILTER: it retains fine contaminants across a very wide
field of actions. It ranges from 3 microns to 10 microns. Efficiency is up to
99% and in order to prevent breakdown of filter we carry out backwashing.

2c.ACTIVATED CARBON ADSORPTION COLUMN:it is employed in

the process of removing organic compounds. It removes colour, taste and
odour in water by process of adsorption. Backwashing is also carried out on
this filter to prevent fouling and breakdown.

2d.ION EXCHANGE RESIN: it is employed to remove ions present in the

water by exchanging positive and negative charge ions. This carries out
cationic exchange and anion exchange until every ion present in the water is
totally removed. This is backwashed to remove impurities accrued from
previous use and the resin can be regenerated by using acid, salt/caustic
soda.

2e. MICRO FILTERS:this is employed for further removal of

microorganisms that escaped the resin. Commonly used are 5micron filter,
1micron filter, 0.5micron filter and 0.2micron filter.

2f.UV STERILIZER: this is employed after using the micro filter to kill or
eliminate microbial life that is less than 0.2micron such viruses. It uses
ultraviolet radiation set at a high wavelength that ranges from 320 to 400nm.

28
WATER ANALYSIS

So many parameters are been analyzed in water depending on the kind of

sample to be analyzed. These parameters include:

1. pH TEST: To be within the range as specified by official monographs

2. CONDUCTIVITY TEST: Ability to conduct electricity due to the
presence of cations and anions.
3. TOTAL HARDNESS TEST: Is the determination of magnesium and
calcium which hardened the water.
4. SULPHATE TEST: Higher level of sulphates in any water source is an
indication of some form of pollution. But if the sulphate concentration is
low, is an indication that the water source is fresh and unpolluted.
5. TEST FOR CHLORIDES: The presence of chlorides significantly
aggravates the conditions for pitting corrosion of metals (including
stainless steels, aluminum, aluminum alloys, and high-alloyed materials)
by enhancing the formation and growth of the pits through an
autocatalytic process.
6. TEST FOR OXIDISABLE SUBSTANCES: To determine the quantity
of organic compounds in the water. Presence of oxidized organic
compounds indicates toxicity to pharmaceutical products and for human
consumption

SPECIFICATIONS FOR RAW WATER AND DEMINERALISED WATER

TEST RAW WATER DEMINERALISED

WATER
pH 6.5 - 8.5 6.5 - 7.5
TOTAL Not more than 500ppm Not more than 100ppm
DISSOLVED
SOLIDS

29
 TOTAL Not more than 300ppm 0 - 60ppm
HARDNESS
CONDUCTIVITY Not applicable Not more than 10µS/cm
CHLORIDES No change for at least 15 No change for at least 15
minutes minutes
OXIDISABLE Solution remains faintly Solution remains faintly pink
SUBSTANCES pink
SULPHATES Solution remains the Solution remains the same for
same for at least 1 hr. at least 1 hr.

7. TEST FOR ALKALINITY: To determine if the water is alkaline.

Alkalinity resists a change in pH, it helps prevent acidic water (pH,<5)
that is harmful to humans, wildlife, and aquatic organisms. Alkaline
compounds not only neutralize acidity, but also react with heavy metals,
such as lead, arsenic, and cadmium, to remove them from the water.
8. TEST FOR ACIDITY: To determine if the water is acidic. Acidic water
is toxic to human, wildlife, and aquatic organisms.
9. TEST FOR TAMC AND TYMC: To determine Total Aerobic
Microbial Count and Total Yeast And Mold Count in Water for
production.
10.TEST FOR PATHOGENS: To check for pathogens that maybe present
in water.

CHAPTER THREE

30
 PRODUCTION PROCESS

3.1TABLET PRODUCTION PROCESS

The manufacturing steps begin with the assembly and pre-weighing of both
active ingredients (API) and excipients (inactive ingredients) in an isolated
room under local exhaust ventilation. the ingredients are moved to a granulation
room. The active ingredients and excipients are mixed. The initial blending of
the ingredients is done in a wet state. At the end of the wet blending process, the
granulation is typically moved to a wet mill, where particles in the mix are
reduced to a specific size. The milled granulation is then dried using a fluid bed
drier. The dried granulation may or may not undergo the addition of a lubricant
before dry-blending and/or dry-milling, depending on the specific product and
process. The final granulation, ready to be made into tablets, is then stored in
sealed containers. The raw materials and granulation, and sometimes the
intermediate products, are typically sampled and assayed by quality-control
personnel prior to being moved to the next process step. When needed, the
granulation is moved to a compression room, where it is made into tablets by
means of a tablet press. Formed tablets exit from the machine through tubing at
the side, and drop into plastic-lined drums. When filled, the drums are sampled
and inspected. After assay by quality-control personnel, the drums are sealed,
stored and staged for packaging operations. Some tablets also undergo a coating
process, in which layers of edible wax and sometimes sugars are used to seal the
tablet.
The tablets are packaged by sealing them in blister packs or bottle depending on
the nature of the product. In this process, the containers of tablets are moved to
the packaging area. The tablets may be manually scooped into the packaging
machine hopper or fed by means of a vacuum wand. The tablets are then either
immediately sealed between layers of aluminium foil and plastic film (blister-
packaging). The blister packs are then conveyed along a line on which they are

31
inspected and placed in pouches or boxed with appropriate inserts. taking
paracetamol(agemol) as case study

PARACETAMOL: It belongs to a group of medicine called analgesics

(painkillers) and is used to treat pain (including headache, toothache ,back and
period pain) and cold or flu symptoms.

Active Ingredients For agemol Tablet: Paracetamol (100kg)

Excipent: gelatin, sodium propyl paraben, corn starch, purified talc and
magnesium stearate

Equipment For The Production: Weighing balance ,Rapid mixer granulator

Fluid bed dryer,Multi-mill machine,Blistering machine

Production Procedure Of Agemol Tablet

1.The paracetamol is weighed, starch and Gelatine were also properly weighed

2.Starch, Gelatin and sodium propyl paraben were prepared with the paste
machine

3.the Api and Excipient were added to the rapid mixer granulator ,then the
paste were added for wet mixing

4. the Agemol granules was immediately discharged in stainless mesh.

5. The lump and clopped granules was taken to the fluid bed dryer in order to be
dried at the temperature of 80 0c for 45-60 minutes.

6.The dried lumped granules were grinded by the multi-mill machine into
uniform or sizes.

7.The Granules were blended in the octagonal blender to have a homogenous

mixture. During blending, purified talc and magnesium stearate are added to

32
serve as lubricants while starch is added for disintegrating and blend for 10
minutes.

8.The dry granules is compressed into the desired shape by tablet compressing
machine that have the weight range of 570-610 mg. The weight of each drug are
written on the tablet by the machine.

9. compressed tablet is taken to the blistering machine to be blistered then

packaged and cartooned.

33
 CHAPTER FOUR
QUALITY CONTROL ANALYSIS
4.1 LABORATORY SAMPLES/ASSAY

A sample is a unit representation of bulk substance taken to know the

composition and characteristics of the large volume of the substance. The
chapter covers:

1. Water treatment and water analysis of deminerlised water/raw water

2. Reagent preparation
3. Sampling analysis for Raw material and finished product tablet

4.1.1a WATER TREATMENT:

In New Age pharmaceutical industry limited, water treatment involves

basically the following operations chlorination, dechlorination, filtration,
adsorption, ion exchange and irradiation.

 METHOD OF CHLORINATION:
Measure 23.2mL of sodium hypochlorite, NaOCl into 3500L of water and allow
to stay for one (1) hour.
 METHOD OF DECHLORINATRION:
Measure 15.52g of sodium meta bisulphite, Na 2S2O3in 3500L of the disinfected
water for one (1) hour.
 METHOD OF FILTRATION, ADSORPTION, ION EXCHANGE AND
IRRADIATION:
This involves passing the dechlorinated water through a coarse sand filter and
then through a fine sand filter to remove both large and small debris or solid
particles. This water now undergoes adsorption in an activated carbon
adsorption column to remove odour, colour and taste. The water is then moved
to the ion exchange to the ions present in the water and from here we have our
demineralized water. Furthermore, this demineralized water is passed through

34
 micro filters of 5µm,2µm, 1 µm, 0.5µm and 0.2µm to remove micro-
organisms.The water is then passed through irradiation by using a UVC
sterilizer to destroy both RNA and DNA viruses present in the water and every
other micro-organism. After this whole processes a purified water is obtained.
Block flow diagram of water treatment in NAPIL (2021)

Chlorination Dechlorination
(For 1 Hour) (For 1 Hour)

Filtration Adsorption
(Coarse Sand Filter And (Activated Carbon
Fine Sand Filter) Adsorption Column)

Demineralized Ion Exchange

Water

Filtration
(5 µm,2 µm, 1 µm,
0.5 µm, 0.2 µm)

Irradiation
Purified Water
(UVC Steriliser)

4.1.1b WATER ANALYSIS OF DEMINERALIZED/RAW WATER

35
A.DETERMINATION OF HARDNESS IN WATER

Hardness in water is contributed by the presence of calcium and magnesium

ions.

Apparatus:Pipette, beakers, conical flasks, pipette filler, measuring cylinder.

Reagents: Eriochrome Black T (EBT indicator) , 0.01M sodium ededate.

Procedure

50ml of sample (water) is measured into a conical flask, followed by 2 to 3

drops of hardness indicator (EBT). This is then titrated with 0.01M sodium
ededate until a bluish color change is observed.

CALCULATIONS

M1V1=M2V2

Where M1-Molarity of Ca2+

V1-volume of water used

M2-molarity of sodium ededate

V2-volume of sodium ededate used

Such that; M1=M2V2/V1

Example; 0.01M ×0.8/50

=0.00016, multiply by the molecular weight of Ca =0.0064

The result gotten should be multiplied by a factor of 1000 to leave it in

milligram per litre (mg/L) or parts per million (PPM).

0.0064 ×1000 = 6.4ppm or mg/L

B.TEST FOR SULPHATES

36
Higher level of sulphates in water is an indication of some form of pollution.

Apparatus: Pipette, pipette filler, conical flask, beaker, measuring cylinder

Reagents : Dilute hydrochloric acid (HCL), Barium chloride solution (BaCL2)

Procedure

Measure 10ml of water into a conical flask. Add 0.1ml of dilute HCL and 0.1ml
of BACL2 solution. If the solution shows no change in appearance for at least 1
hour, it shows that there are no sulphates in the water.

C.TEST FOR CHLORIDES

Presence of chlorides corrodes the metals.

Apparatus: Pipette, pipette filler, conical flask, beaker, measuring cylinder

Reagents: Dilute HNO3 and silver nitrate solution

Procedure

Measure 10ml of water into a conical flask. Add 1ml of dilute HNO3 and 0.2ml
of silver nitrate solution. If the solution shows no change in appearance for at
least 15 minutes, it shows that there are no chlorides in the water.

D. TEST FOR OXIDISABLE SUBSTANCES

Presence of oxidized organic compounds indicates toxicity to pharmaceutical

products and human consumption.

Apparatus: Pipette, pipette filler, measuring cylinder, conical flask, beaker, hot
plate, fume cupboard

Reagent: Dilute sulfuric acid, and 0.02M KMnO4

Procedure

37
100ml of water is measured into a conical flask. Add 10ml of dilute sulfuric
acid and 0.1ml of 0.02M KMnO4 and boil for 5 minutes. If the solution remains
faintly pink, it indicates that there are no oxidisabl substances in the water.

E. TEST FOR ALKALINITY

To determine if the water is alkaline

Apparatus:Pipette, pipette filler, measuring cylinder, conical flask, beaker

Reagents:Bromothymol blue solution

Procedure

Measure 10ml of freshly boiled and cooled water into a conical flask. Add
0.1ml of bromothymol blue solution. If the solution is blue, it indicates
alkalinity.

F. TEST FOR AICIDITY

To determine if the water is acidic

Apparatus: Measuring cylinder, pipette, pipette filler, conical flask, beaker

Reagents: Methylred solution

Procedure

Measures 10ml of freshly boiled and cooled purified water into a conical flask,
and add 0.05ml of methylred solution. If the solution is red, it indicates acidity.

4.1.2 LABORATORY REAGENTS

These include stock chemicals which can either be solid or liquid from which
other solutions of known concentration can be prepared from. Such prepared

38
solutions include volumetric solutions, bench solutions, standard solutions, e.t.c.
the concentration of these solutions come in different units e.g. mol/dm3, %,
ppm, N, and so on.

The formula for preparing each solution depends upon the unit of its
determination

For Molarity= moles of solute

Volume of solvent

For Molality= moles of solute

Kilograms of solvent

For Normality = number of mole equivalent

1 litre of solution

% concentration = x * molar mass*required volume(weight pervolume)

100*1000

examples of volumetric solutions are 0.1M HCl, 0.1M NaOH, 0.02M KMnO4,
etc

4.1.3 SAMPLING ANALYSIS FOR RAW MATERIAL AND FINISHED

PRODUCT TABLET

4.1.3a Identification Test of Raw Material

Pharmaceutical raw material comes in bags, kegs, drums and containers. The
raw materials are receive based on the following criteria, product name,
manufacture’s address, country origin, manufacturers date and expiry date,

39
 gross and net raw materials of both the API and the excipent. These tests are
carried out on samples to know whether the compound used in manufacturing
the product as claimed by the manufacturer are present or not and also to know
if the product contains any harmful/impurities compound.

Analysis of Raw Material

For Raw material to be approved for production, it has to undergo some

chemical analysis both qualitatively and quantitatively. These analyses test for
its physical appearance, solubility( in both water and Ethanol), Moisture
content, Melting point/ boiling point, pH range, % purity, % Content. As in case
study of paracetamol powder

1. Paracetamol (C8H9NO2)

Physiological Properties

Action: pain reliever (Analgesic)

Physical properties
i. Paracetamol powder is white crystalline powder
ii. paringly soluble in water and freely soluble in ethanol
iii. The sample melted at the normal melting range of 680-720oC

2. METRONIDAZOLE (C6H9N3O3)

40
Action: Antibacterial
Physiological properties
* White or slightly yellowish crystalline powder
* Slightly soluble in water and ethanol
* Melting Point 159-163oC
*Moisture content 99.0%-101.0% (dried substance)
Assay Procedure
* 0.23g of metronidazole benzoate was weighed into a conical flask
* It was dissolved in 100ml of anhydrous acetic acid
* A drop of crystal violet (indicator) was added
* It was titrated with 0.1M perchloric acid
Note (each 1ml of 0.1M perchloric acid is equivalent to 17.12mg of C6H9N3O3)
% Assay = Titre value X Equivalent weight X100
Weight of Metronidazole

4.1.3b FINISHED PRODUCT ANALYSIS

 ASSAY ON PHARMACEUTICAL PRODUCTS

Assay of finished product is an investigative procedure in the laboratory

analysis for quantitatively measuring the presence or amount of a target entity.
The measure entity is generally called the analyst.

After the identification test is carried out on the drug sample, it is said that the
drug must pass the assay test in addition to the physical parameter test before
the issuance of the drug. The aim of these analyses is to quantify the amount of
active pharmaceutical ingredient present in the drug sample. The method of
analysis used by the analyst in the analyzing of these drugs is usually reviewed
from the S.O.P (Standard Operating Procedure). The S.O.P is gotten B.P which
is standard compendia for the preparation and analysis of drug. The acceptable

41
limit for Active ingredient that must be present in the drug sample is between
95%-105%.

1. PARACETAMOL ASSAY

AIM

To determine the proportion of paracetamol in Agemol tablet

APPARATUS

Weighing balance, conical flask, Petri dish, pipette, pipette filler, measuring
cylinder, mortar, pestle, filter paper

PROCEDURE

Weigh and powder 20 tablets, add a quantity of the powder that contains 0.15g
of paracetamol to 50ml of 0.1M NaOH and dilute with 100ml of water. Shake
for 15 minutes, and add sufficient water to produce 200ml. mix, filter, and
dilute 10ml of the filtrate to 100ml with water. Add 10ml of the resulting
solution to 10ml of 0.1M NaOH, dilute with 100ml of water and measure the
absorbance of the resulting solution at the maximum of 257nm.

Calculate the content of C8H9NO2 taken 715 as the value of A(1%. 1cm) at the
maximum of 257nm.

CALCULATIONS

Product: Agemol tablet

Label claim: 500mg

% content: 95%-105%

Label range: 475mg-525mg

Calculation for weight taken:

595ml-500mg

42
 X=150mg

X=595x150/500

X=179mg=0.179g

Mg / label claim = dilution factor x Absorbance x average weight x 1000/weight

taken x E1

% content = mg / label claim x 100/ label amount

2. IBUPROFEN ASSAY

Ibuprofen is a non-steroid anti inflammatory disease, is one of the most

common used medication for effective relief of pain and inflammation caused
by many conditions such as headache, toothache, back pain, arthritis, menstrual
cramps, or minor injury.

AIM

To determine the proportion of ibuprofen in Ibuage tablet

APPARATUS

Weighing balance, conical flask, pipette, pipette filler, resort stand, burette,
funnel, measuring cylinder

PROCEDURE

Dissolve 0.18g (0.585g) of ibuprofen powder in 100ml of ethanol (96%) and

titrate with 0.1ml NaOHvs, using phenolphthalein (0.2ml) as indicator until a
pinkish-red color is produced. Repeat the procedure without the substance to get
the blank.

Each ml of 0.1M of NaOHvs, is equivalent to 20.63mg of C13H18O2.

CALCULATIONS

Product: Ibuage tablet

43
Label claim: 400mg

% content: 95%-105%

Label range: 380mg-420mg

Calculation for weight taken (x): 520mg = 400mg (ibuprofen)

X = 450mg

X = 520 x 450/ 400 = 585mg = 0.585g

1ml of 0.1M NaOH used = 0.1 / 1000 x 206.3 = 0.02063

Mass of C13H18O2 used = titre value x 0.02063

% content = mass of C13H18O2 used/ average weight x 100

Mg / label claim = % content / 100 x label amount

 WEIGHT VARIATION

During weight variation the ompressed tablet(20 tablet) are weighed to have a
total weight,average weight and individual weight for each tablet. In the case of
paracetamol tablet we take 5 % variation from these ,we calculate the mean
weight to determine the upper and lower limit of the tablet.in case were three set
of the tablet does not correspond with the upper and lower limit,then tablet is
considered failed.

 DISSOLUTION TEST

Dissolution test rate tend to explain the actual time of absorption of a tablet or
the bioavailability of the tablet in the human system. It is carried out using
dissolution test apparatus with different medium for different tablet.the limit for
these test is not less than 80%.

44
 CHAPTER FIVE

5.1 CHALLENGES ECOUNTERED

Industrial training experience in an organization with great expectation from a
student with no remuneration is a great challenge. The challenges encountered
are but not limited to the following:
1. Securing a place for attachment within the required period was a bit
difficult.
2. Waking up very early in order to make it to work on time due to distance
was quite challenging.
3. The company which has no government support did not make provision
to pay IT students nor did they draft any allowance packages so as to
lease the expenses for the six months program.

5.2CONCLUSION

At the end of my industrial training, I have learnt the types of analysis done on
water and its importance. I also learnt the consequences of determined
parameters, various assays done on pharmaceutical products and the basic
concepts of quality control techniques of pharmaceutical industries.i have also
learnt water treatment and production of solid/tablet oral dosage. However, this
training afforded me the opportunity to develop embedded creative and thinking
skills. It has brought to life ideas that were formally written down, also giving
room for me to think big in a unique way.

5.3 RECOMMENDATION

I hereby recommend that the following should be done to help and ease
problems encountered during SIWES;

45
1. The company should be supported by government in order to be able to
make adequate provision for the training of industrial training students.
2. The company should take note of any faulty equipment in the laboratory
and follow it up immediately.
3. Institutions should make proper arrangements for SIWES placements and
should follow it till end.
4. The company should be supported in order to continue to be willing to
accept and encourage student that are seeking for SIWES placement in
their company.

46
REFERENCE

“Pharmaceutical manufacturers Association V. The president of south Africa

(PMA)”, 2002 (2) SA 674 (CC) (S. Africa)
Cole, G. 1990. Pharmaceutical Production Facilities: Design and Applications.
Chichester, West Sussex: Ellis Horwood Ltd.
FDA History-part II

Gennaro, A. 1990. Remington’s Pharmaceutical Sciences, 18th edition. Easton,

PA: Mack Publishing Company.

Goldzieher, MA and JW Goldzieher. 1949. Toxic effects of percutaneously

absorbed estrogens. JAMA 140:1156.

Hardman, JA Gilman and L Limbird. 1996. Goodman and Gilman’s The

Pharmacologic Basis of Therapeutics. New York: McGraw Hill Co.

Naumann, B, EV Sargent, BS Starkman, WJ Fraser, GT Becker and GD Kirk.

1996. Performance-based exposure control limits for pharmaceutical active
ingredients Am Ind Hyg Assoc J 57: 33-42. 1996.

Outsourcing-pharma.com

Perry, R. 1984. Perry’s Chemical Engineers’ Handbook. McGraw- Hill Inc.

New York, NY. 1984.

Quality Control Department Of New Age Pharmaceutical Industry.

Sargent, E. and G Kirk. 1988. Establishing airborne exposure control limits in

the pharmaceutical industry. Am Ind Hyg Assoc J 49:309-313.

Significant Dates in US Food and Drug law history

Sneader, Walter (2005). Drug Discovery, A history New York: Wiley. P.371

Swarbick, J and J Boylan (eds.). 1996. Encyclopedia of Pharmaceutical

Technology. New York: Marcel Dekker, Inc.

www. Researchandmarkets.com/research/46d237/Indian-pharmaceutical

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