Industrial Training Report SEP 2019

PREFACE

Pharmacy is the Art and Science of preparing and dispensing drug. It is the health profession
that links health sciences with chemical sciences and aims to ensure the safe and effective use
of pharmaceutical drugs. So it is a fully technical profession where practical knowledge is
much more important along with theoretical knowledge.

According to curriculum of a four year integrated degree course of BACHELOR OF

PHARMACY each student has to undergo practical training for a periods of four week in
various pharmaceutical industries in India.

I was directed to undergo my industrial training at CHIROS PHARMA and this report
contains a brief description of the above pharmaceutical industry which was observed during
the training program. INDUSTRIAL TRAINING 2019.

1. INTRODCTION
In India the pharmaceuticals sectors is one of the most developed hi-tech sectors which are
contributing in the country’s economy. After the promulgation of Drug Control Ordinance
1982, the development of this sector was accelerated. The professional knowledge, thoughts
and innovative ideas of the pharmacists working in this sector are the key factors for these
developments. Due to recent developments of this sector it is exporting medicines to global
market including European markets. This sector is also providing 97% of the total medicine
requirements of the local market. Leading pharmaceuticals companies are expanding their
business with the aim to expand export market. There are many industries that have been
established with the high tech equipment’s and professionals which are working to enhance
the strength of this sector. CHIROS is one the leading companies in pharmaceuticals sector.

CHIROS PHARMA had been established in the year 2010 which is , an ultramodern , WHO-
GMP certified company for manufacturing of specified / specially pencillin and
cephalosporin oralsolid dossage forms which includes stable clavulanic acid combinations .

Chiros Pharma is an manufacturer , supplier and exporter of clavulanic acid combination and
beta lactum products.

Chiros Pharma is serving to manufacturer beta-lactum products for both Export and Domestic
markets and its unit is approved by CDDA Srilanka, PPB Kenya and NAFDAC Nigeria, and
TFDA Tanzania .

Chiros Pharma currently hold registration for export of products in South East Asia and
African countries and continuously expanding for other regions .

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Chiros Pharma serves in domestic market to several companies like Zydus, Cadila, Biochem,
German Remedies , Wanbury, Tablets India, Pharmed, Corona, Invision and many more .

ENVIRONMENTAL HEALTH SAFETY

At chiros Pharma, they are fully commited to achieving excellence in environment , health
and safety (EHS) and conduct our activities in the most manner. The importance of EHS is
continually stressed and extensively promoted as a part of our corporate culture.

The implementation of the ESH policy is ensured by institutionalizing a robust ESH

Management System , adequately supported by a well- defined organizational structure.

1.1 COMPANY PROFILE:

GENERAL INSTRUCTIONS AND PRECAUSIONS:

 Ensure area and equipment cleanliness before starting the manufacturing operations.

 Check and ensure that all manufacturing equipment and other required accessories are
clean ready for use.

 Wear gloves and nose mask during all manufacturing process.

 Counter check the weights of all ingredients before using in the batch

 Get line clearance from QA for manufacturing.

 Air handling unit (AHU) system should be kept ON throughout the manufacturing process.

 Temperature should be kept between 25ºC ±2ºC and relative humidity should be kept
between 50±10%.

 Ensure that only QC approval purified water is being used for manufacturing purpose

 Always transfer solution to the manufacturing vessels through 20 meshes.

 During the preparation of this product, no other product processing should be done in the
same area.

 Whenever sifting through SS mesh is involved; check the mesh integrity before and after
use.

 All critical aspects during manufacturing like temperature, duration of mixing, weight, etc.
must be checked and recorded by the supervisor.

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 Supervisor to ensure completion of all in-process records during various stages of

manufacturing operations till completion of the batch.

 Release from QA should be taken from all in-process tests mentioned in batch
manufacturing record

 No over writing is allowed in batch manufacturing record. If initial data is wrong entered,
cancel the data by single stroke arrow and put initials.

 All the details whatever is necessary should be recorded in batch manufacturing record
(BMR).

 Send a test request form to QC after manufacturing is completed

 Check all polyethylene bags before and after material loading for black particles and
sealing.

 Check calibration of respective equipment/machine before use.

PRODUCTION
Raw material Manufacturing Packaging

QUALITY CONTROL

Raw material Testing of material Evalution parameter

QUALITY ASSURANCE
Documentation

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1.2 PRODUCTION AREA

Tablet section Tablet component and diluents

Active Ingredient: Pencillin and cephalosporin derivatives like: Cefixime, Cefpodoxime

Proxetil, Potassium Clavulate, Azithromycin, Cefixime trihydrate, Ofloxacin , cefuroxime
Axetil, cednir , amoxicillin etc.

Non active Ingredient

• Diluents lactose, starch, mannitol etc

• Binder acacia, gelatin, tragacanthetc
• Lubricants stearic acid, magnesium stearate, talc etc
• Disintergrants starch are the most commonly use Disintergrants agents Color &
Flavor agents

Method of preparation

They are three method of preparation of tablet

A. Wet granulation

B. Dry granulation

C. The direct compression process

A. Wet granulation: The most widely used process of agglomeration in pharmaceutical

industry is wet granulation. Wet granulation process simply involves wet massing of the
powder blend with a granulating liquid, wet sizing and drying. Important steps involved
in the wet granulation i) Mixing of the drug(s) and excipients ii) Preparation of binder
solution. iii)
Mixing of binder solution with powder mixture to form wet mass.
Iv)Drying of moist granules

v) Mixing of screened granules with disintegrant, glidant, and lubricant.

vi) Tablet compression

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B. Dry granulation: In dry granulation process the powder mixture is compressed

without the use of heat and solvent. It is the least desirable of all methods of granulation. The
two basic procedures are to form a compact of material by compression and then to mill the
compact to obtain a granules. Two methods are used for dry granulation. The more widely
used method is slugging, where the powder is recompressed and the resulting tablet or slug
are milled to yield the granules. The other method is to precompress the powder with
pressure rolls using a machine such as Chilosonator

C. The direct compression process : This method is used when a group of

ingredients can be blended and placed in a tablet press to make a tablet without any of the
ingredients having to be changed. This is not very common because many tablets have active
pharmaceutical ingredients which will not allow for direct compression due to their
concentration or the excipients used in formulation are not conducive to direct compression.
Granulation is the process of collecting particles together by creating bonds between them.
There are several different methods of granulation. The most popular, which is used by over
70% of formulation in tablet manufacture is wet granulation. Dry granulation is another
method used to form granules.

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Dispensing of raw material - dispensing of raw material done in reveres laminar air
flow only approved raw material is dispense

MATERIAL OF CONSTRUCTION: Main body:-Stainless Steel PVC coated

PRE FILTER (PRIMARY FILTER): Filter Casing S.S.304/316 flange type. Efficiency
90% down to 10 micron (EU 4 Rating.) Media Three layers of High Density Polyethylene
Mesh along with AL.wiremesh.

INTERMIDIATE FILTER (SECONDRY FILTER: Filter Casing S.S.304/316 flange

type Efficiency 95percentage down to 5 micron (EU 7 Rating.) Media Non woven synthetic
media sandwiched between two layers of HDPE mesh.

SUPPLY FILTER: Filter Casing Aluminum factory extruded section, Box type.
Efficiency 99.999percentage down to 0.001-micron (EU 14 Rating) Media Micro fiberglass
paper media (Imported) pleated along with Hot Melt Glue.

EXHAUST FILTER: Filter Casing Aluminum factory extruded section. Efficiency

99.999percentage down to 0.001-micron (EU 14 Rating) Media Micro fiberglass paper
media (Imported) pleated along with Hot Melt Glue.

BLOWER MOTOR ASSEMBLY: Electric Motor Compton / Shanty make, double ended
shaft, Single phase, 240 volts, 50Hz. Impellers Aluminum statically & dynamically balanced,
forward curve type. Blower casings FRP,centrifugal type with spring suspension.

ACESSORIES: Magnehelic pressure gauge for checking the pressure drop across the supply
Minipleat HEPA Filters and pre filter. Range 0 TO 50 mm of WC.

ELECTRICALS: Feather touch ON/OFF switches for b/w motor, tube light, UV light &
aux. socket with light indication. 40w, Fluorescent light with milky diffuser. 6/16 Amps,
Aux. socket with s.s.cover plate. 16 Amps. Three pin top along with connection cable

Fig- Reverse Laminar Air Flow

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Procedure

Before the operation of dispensing both, warehouse and

QA personnel or their trained personnel must ensure the
following:

• Dispensing Area and equipments are cleaned.

• The waste bin must be clean & closed properly.
• Temperature and Relative Humidity of dispensing area are within the specified limit.
 All the logbooks of the respective areas are updated.
• The RLAF i.e. “Reverse Laminar Air Flow” is switched “ON” by pressing button on
the panel 15-20 minutes before the dispensing activity starts.
• Wait until the pressure differential across the HEPA filter comes within the limit.
• If any abnormal noise or problem in instrument is observed then inform the
engineering department for its repairing.
• After achieving required differential pressure of gauge then allow for further
dispensing activity.
• Fill the differential pressure at start of shift
• After completion of activity switch off the RLAF and mains electric supply.
Remove the powder present. Affix the “TO BE CLEANED” label duly filled and
signed.
• Fill the dispensing operation details in Sequential Equipment logbook.

GRANULATING DEPARTMENT

SIEVER VIBRATOR SEPERTOR IS USED TO SIEVING OF PARTICLE

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FIG-VIBRATOR SIEVER

Rapid Mixer Granulator (RMG):- Rapid Mixer Granulator is a multi-purpose processer

equally suitable for high-speed dispersion of dry powders, aqueous or solvent granulation,
and effervescent products and melts pelletization.

Fig –Rapid mixture granulator

Wet granulation is a common step in the manufacture of many solid dosage pharmaceuticals.
Wet granulation can be accomplished in a mixer granulator. A mechanical impeller moves the

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powder while a liquid binder is applied onto a moving powder bed. Addition of the liquid
binder starts the formation of granules. The granulator also has a chopper.Impeller and
chopper are mainly responsible for wet granulation in the rapid mixer

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granulator. Rapid Mixer Granulator is designed to achieve excellent mixing and consistent
granules at lower operating cost along with higher productivity. Better mixing and closed
control of granule size leads to faster tableting speeds with improved quality and least
rejections.

Working Principle: The Rapid Mixer Granulator is mixing unit with a bottom entry agitator
ad side mounted chopper for granulation. It is used for dry blending, wet mixing, preparation
of dough and granulation, i.e. cutting of the wet mass into small size granules. It works on the
basic principle of agitation of the contents of the bowl at moderate speed and then running a
specially profiled cutter blade at high speeds into the wet mass.

The granulation is conventionally performed in the following process steps:

• Mixing of dry material at high impeller and chopper speeds for a few minutes.

• Addition of liquid binder by pouring it on to the powder, while both the impeller and
chopper are running at a low speed.
• Wet massing with both agitators running at high speed.

Impellers: Impellers are fixed at the bottom of dome shaped stainless steel bowl. It has fully
length and two half-length blades. Impellers are designed such a way that small blade lift the
material and full-length blades push the material to mix well. These impellers break up the
wet mass into small pieces and granules.

Chopper: These are specially designed small blades located at the bottom of the dome. The
primary function of chopper is to cuts the lumps into smaller fragments those are mixed
equally by impeller and aids the bowl or sprayed onto the powder to achieve a more
homogeneous liquid distribution. It rotates at high speed (1440/2880) RPM to give easy and
uniform granulation. The speed of chopper is responsible for the size of granule. Chopper

does not have any significant effect on the granule size when impeller speed is high (above
200 RPM).

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Discharge Port: The discharge port is mounted horizontally into the dome with vertical
downward opening. Granules are unloaded in the container through the discharge port.
Opening of discharge port is operated by pneumatic cylinder (compressed air cylinder) that
requires 3-5 kg/cm2 pressure of compress air

Fluidized Bed Dryer

DECRIPITION

In a fluid bed dryer, good contact between hot air and particles to be dried so obtained
which causes rapid drying.
Theory: If a gas is allowed to flow up wards through a bed of solids particles at a velocity
greater than the setting velocity of the particles, the particles are partially suspended in the
gas stream.

The resultant mixture of solids and gas behave like a liquid and the solids are said to be
fluidized. The drying gas with the result that the drying takes place in a much shorter period
surrounds each individual solid particle.

Two types of fluidized bed dryers are used in the pharmaceutical industry. There are

1. Vertical fluidized bed dryers

2. Horizontal fluidized bed dryers

PRINCIPLE
In the fluidized bed dryer, hot air or gas is passed at high pressure through a perforated
bottom of the container containing granules to be dried.
The granules are suspended in the stream of air and are lifted from the bottom. This condition
is called fluidized state.

The hot air is surrounded every granules to completely dry them. Thus materials or granules
are uniformly drying.

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CONSTRUCTION

Two types of fluidized bed dryers are available in the pharmaceutical industry. There are
vertical fluidized bed dryers and horizontal fluidized bed dryers.

The construction of the vertical fluidized bed dryer is made up of the stain less steel or
plastic. A detachable bowl is placed at the bottom of the dryer, which is used for charging and
discharging of the materials.

The bowl has a perforated bottom with a wire mesh support for placing the

for the charging materials to be dried. A fan is mounted in the upper part for circulating hot
air. Fresh air inlet, prefilter and heat exchanger are connected serially to heat the air to the
required temperatures.

The temperature of the hot air and exit air are monitored. Bag filters are placed above the
drying bowl for the recovery of the fines.

The air flow is adjusted by means of recirculation control and fabric bags are provided to
prevent the passage of the fine particles. This type of the fluidized bed dryer is a batch type
dryer and the drying chamber is removed from the unit and dumping.

The different capacities ranging from 5 kg to 200 kg with an average drying time of about 20
- 40 min of the fluidized bed dryers are available

Horizontal vibrating conveyer fluidized bed dryers are used for continuous drying of a large
volume of the materials.

WORKING

The wet granules to be dried are placed in a detachable bowl. The bowl is pushed in to the
dryer. Fresh air is allowed to pass through a prefilter, which subsequently gets heated by
passing through a heat exchanger.

The hot air flows through the bottom of the bowl. Simultaneously fan is allowed to rotate.
The air velocity is gradually increased. When the velocity of the air is greater than the settling
velocity of granules, the granules remains partially suspended in the gas stream.

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After sometimes a point of pressure is reached at which the frictional drag on the particles is
equal to the force of the gravity. The granules rise in the container because of high velocity
gas 1.5 to 7.5 m per min and later fall back in a random boiling motion.

This condition is said to be fluidized state. The gas surrounds every granules to completely
dry them. The air leaves the dryer by passing through the bag filters. The entrained particles
remain adhered to the inside the surface of the bags. Periodically the bags are shaken to
remove the entrained particles.

Intense mixing between the granules and hot gas is provided uniform conditions of the
temperature, composition and particle size distribution. Drying is achieved at constant rate
and falling period is very short. Any attempt to increase the air velocity may result in
entrainment.

The residence time for the drying is about the 40 min. the materials is left for the sometimes
in the dryer for reaching ambient temperature. The bowl is taken out for the discharging. The
end product is free flowing.

Fig –fluidized bed dryer

PHARMACEUTICAL APPLICATIONS

• It is used for the popularly drying of the granules in the production of the
tablets.

• It is used for the three operation such as mixing, granulation and drying.

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Double cone blander

Principle

The main body of the blender consists of two cone-shaped sections welded at their bases to a
central cylindrical section. The axis of rotation is perpendicular to the cone axis and passes
through the cylindrical section. The driving motor is located at one of the two lateral supports
holding blender body. The solids are introduced into the blender through the loading aperture.
In this type of blender, mixing takes place axially, as a result of the powder moving through
the different sections. Mixing is thorough but it depends on the rotating speed

Fig –double cone blander

Procedure:-

• Make sure that Line clearance is duly checked and signed by QA Personal as per
SOP clean before carry out the process

• Adjust the angle of the blender with the help of a moving wheel to a required position
for convenience in loading the materials.

• Load the materials from the container to the blender as per the sequence specified in
the individual Batch Manufacture Record (BMR)

• After loading the materials, close the lid of the blender.

• Put the safety pin on the lid and fit it properly within its groove. Lock the blender lid
by moving the wheel in clockwise direction.

• Before starting the operation, ensure that the lid and the safety pin lock has been
assembled properly.

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• Put the safety guard before commencement of the operation.

• Switch on the equipment and note down the starting time.

• Blend the material as per the time specified in the individual BMR.

• To unload the material, Ensure that the equipment is put off.

• Remove the safety guard.

• Adjust the position of the blender at the required angle for convenience in unloading
the materials.

• Unlock the safety pin and remove the lid from the blender.

• Unload the blended materials.

Rotary tablet press machine

A rotary is one of the most popular type machines. Normally, we use this machine for high
production of tablets

Parts of Rotary Tablet Press Machine

• Hopper; holds powder you intend to press

• Die cavity; it determines the size, type and texture of tablets

• Feed paddle; directs material into the die cavity

• Punches & dies; they help to compress powder into tablets  Cam tracks; they
guide the upper and lower punches.
• Capacity controls; it ensures proper filling of the die cavity

• Compressors; they may include pre-compression and main compression systems. This
compresses the powder into a desired tablet.
• Ejection cam; this helps to remove tablets from the die cavity

• Take-off blade; deflects tablets into discharge chute

• Control system; controls and coordinates most functions of the machine Stage of
rotator tablet machine

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1 Powder Filling Stage

At this stage, feed the tablet press machine with powder.

That is, place your powder in the hopper from where it will flow to the tooling system of the
machine ready for compression.

Due to the geometrical shape of all hoppers, this powder will flow to the tablet press tooling
system.

2 Powder Metering Process

Tablet process involves precise filling and compression of powder in the die cavity.
Therefore, the machine should move excess powder that may be the source of any form of
inconsistencies.

At this stage, your rotary tablet press machine should ensure the accurate filling of the die
cavities.

This should include the desired volume and weight of powder that should be compressed into
tablets.

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Four critical steps in tablet making process

During this process, the lower cam of the turret moves upwards to a predetermined level.

This results in excess powder that is scraped from the die surface.

3 Tablet Compression Process

Rotary tablet press” from the fact that it has a rotating turret.

It is this turret that holds the tablet tooling system.

Normally, the production capacity depends on the size of rotary tablet press machine‟s turret.

In most cases, you may divide turret into the following key sections:

 Upper turret; section that holds upper punches  Lower turret; part that
holds lower punches  Die table; a section that holds dies

With the powder filled in the dies to the right depth, the upper and lower punches begin to
compress the powder.

This is how the process goes:

Normally, the upper and lower punches exert a predetermined amount of pressure that
compresses tablets to the right size and depth.

The pre-compression process removes any traces of air that might be within the powder
particles.

From the pre-compression stage, it then moves to the main compression.

The main compressor exerts significant amount of force that compacts powder to a desired
thickness and hardness. This is due to the pressure that is exerted on the punches by a series
of pressure rolls. Remember, this is a continuous process where the turret moves the in a
rotary manner. Normally, a complete revolution should produce the exact number of tablets
as the number of dies on the turret.

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4 Tablet Discharge
At this stage, the upper cams will pull the top punches back to their initial position. On the
other hand, the lower punches are lifted up. As a result, the lower punch pushes the already
processed tablets out of the die cavity. The scraper will then remove the tablet from the
compression machine to the discharge chute. Basically, this will mark the end of one
complete cycle of the tablet compression machine

Fig –Rotary tablet compression machine

COATING OF TABLET

Tablet coating can be described as a process of applying an edible paint on the surface of a
pharmaceutical dosage form to achieve specific benefits. This is an additional process in
tableting which causes an increase in the cost of tablet production

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Objectives of coating

• The objectives of tablet coating are as follows:

• To mask the disagreeable odor, color or taste of the tablet.

• To offer a physical and/or chemical protection to the drug.

• To control and sustain the release of the drug from the dosage form.

• To incorporate another drug which create incompatibility problems

• To protect an acid-labile drug from the gastric environment.

• Increasing the mechanical strength of the dosage form

PROCESS OF COATING

Sugar coating

Tablet coating developed originally from the use of sugar to mask the taste and provide an
attractive appearance to at the core.

Film coating

As the sugar coating process is very time consuming and is dependent on the skills of the
coating operator, this technique has been replaced by film coating technology. The process
involves spraying of a solution of polymer, pigments and plasticizer onto a rotating tablet bed
to form a thin, uniform film on the tablet surface.

Film Coating Requirements

The basic requirements for film coating need to be considered independently of the actual
equipment being used. These include the most appropriate means of atomizing the spray
liquid during application, proper mixing and agitation of the tablet bed, and providing enough
drying heat air to evaporation

 Is it important to mask the taste, odour or colour of the tablet?

 Is it important to control the release of the drug?

 What are the specifications that need to be fulfilled during the developmental stage? (size,
colour, shape)

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The tablet to be coated make continuous complicated orbital motion the closed rotating
Drum under the action of a streamline of Baffles. During the motion coating medium
automatically sprays according to the technological process and rational technological
parameters, at the same time hot filtered air supplied under a negative pressure. The hot air
penetrates through the tablets core layers and is discharged from the bottom of the layers,
so that the coating medium sprayed on the surface of the tablet cores will dry rapidly and
evenly, thus forming a solid and smooth surface film on tablet. The whole process is
finished under the automatic by PLC Controls with touch screen Interface.

FIG-COATING APPARTUS

1. PACKING OF TABLET

Packing is the technology of enclosing or protecting product for distribution, storage, sale,
and use. Packaging is also refers to the process of designing, evaluating, and producing
packages. Packaging can be described as a coordinated system of preparing goods for

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transport, warehousing, logistics, sale, and end use. It is sometimes convenient to categorize
packages by layer or functions.

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i. Primary Packaging
ii. Secondary Packaging
iii. Tertiary Packaging

TYPES OF PACKAGING

Blister Packing:

This is useful for packaging of unit dose of pharmaceuticals. This packing mode has been
used extensively for several good reasons. It is a
packaging configuration capable of providing
excellent environmental protection, coupled with an
aesthetically pleasing and efficacious
appearance. It also provides user functionally in terms
of convenience, child resistance and now
temperature resistance. The blister package is formed
by heat softening a sheet of thermoplastic resin
and vacuum drawing the softened sheets of plastic
into a contoured mould. After coming, the sheet is released from the mould and proceeds to
the filling station of the packaging machine. The semirigid blister previously formed, is filled
with the product and lidded with a heat sealable backing material. The backing material can
be either a push through or peelable type. For a push through type of blister, the backing
material is usually heat seal coated aluminum foil.

Strip Packing:

The strip packing is done by aluminum foil or glassine poly paper. A strip package is formed
by feeding two webs of a heat sealable flexible film through either a heated crimping roller or
a heated reciprocating platen. The product is dropped into the pocket formed prior to forming
the final set of seals. A continuous set of packets is formed, generally several packets wide
depending on the packaging machine’s limitations. The strip of packets is cut to the desired
number of packets in length. The strips formed are usually collected and packed into a
folding carton. The product sealed between the two sheets of film usually has a seal around
each tablet, with perforations usually separating adjacent packets.

Bulk Packing:

The packaging of the final product is done in paper cartons, manually, and is finally sealed
using an automatic sealer. The machine can seal cartons.

 AluAlu packaging

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Fig:- alu alu packaging

AluAlu packing contain both side polyvinylchloride foil

3.2 PACKING MACHINERIES

 Accumulating and collating machine

 Blister packs, skin packs and vacuum packing machines

 Converting machine

 Filling machine

 Linear vibrator

 Coding, printing, marking, stamping and imprinting machine

 Package filling and closing machine

 Palletizing, depalletizing, unit load assembly

 Packing sealing machine

 Conveyor belts

 Label dispenser: Domino printer

 Weighing machine: check weigher

 Wrapping machine

 Carton machine

 Other specialty machinery: Slitters, perforating, laser cutters,

1. IMPORTANCE OF QUALITY CONTROL:

The quality in the pharmaceutical industry has become a major concern and there has been a
growing awareness for the significance of the quality of the pharmaceutical products.

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The current concept of Good Manufacturing Practices (cGMP) emphasizes that the quality of
pharmaceutical products must be constructed during the overall process cycle.

Quality Control department plays an important role since it demands the acquisition of
reliable analytical data. Many important decisions are based on the analytical data of quality
control department and it is important to have indication of the quality of these results.

The current Pharmaceutical Industry is facing challenges for the manufacture of Chemical
and Biological drugs for human consumption. Stringent GMPs are being followed for Oral
Drugs (Solid Dosage Form).

This has resulted into improvisation of systematic manufacturing and marketing of safe,
efficacious and qualitative drugs.

With the growth of industry, the legislations from each region have become more and more
complex and created a demand for the need for regulatory professionals to understand and
solve the critical quality control issues in the Pharmaceutical Industries around the globe.

WORKING OF QUALITY CONTROL DEPARTMENT

1. For Raw and Packaging Material Inspection

2. For Finished Products Inspection

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3. For In-process Checks Inspection

Quality control can be defined as day to day control of quality within the company. They are
responsible for the acceptance or rejection of incoming raw material, packing components
and finished products, for the myriad of in process tests and inspections, to assure that system
are been controlled and monitored for the approval and rejections of complete dosage.

Area Limit
1. Chemical Laboratory 25 ± 5°C
2. Instrument Room 25 ± 5°C
3. Microbiology Laboratory 25 ±3°C
4. Packing Storage Room 25 ± 5°C
5. Chemical Storage Room 25 ± 5°C
6. Control Sample Room 25 ± 5°C

The quality control function in an organization normally consist of at least three primary units
–

 Analytical control
 Microbial control
 Packaging control

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ACTIVITY OF QUALITY CONTROL DEPARTMENT

The quality control system operating in our plant ensures that only materials meeting our
specification are Issued for manufacture of products likewise it is ensured that the process
moves from one stage to next stage only if it complies with the in process specification.

i) Sample analysis of all raw materials, bulk products packed materials and finished product.

ii) Quality review (stability study) of finished products

iii) Handling of references substance and working standards.

DOCUMENT MAINTAINED IN Q.C. DEPARTMENT

i) Raw material analysis / Report

ii) Water analysis report (Chemically & biologically)

iii) Intermediate finished product report (blend)

iv) Finished product report

v) Certificate of Analysis: raw material & finished product

vi) Working reference standard report

vii) Calibration report

Viii) Retest report for raw material

ix) Retest report for expired finished product

x) Destruction report

xi) Packing material report.

xii) Rejection Notes of rejected materials.

INSTRUMENTS USED IN Q.C. LAB

1. Analytical balance (METTLER TOLEDO)

2. UV Spectrophotometer (CAMAG)

3. Polarimeter (RUDOLPH, Autopol VI)

4. Karl FischerTitrator (METROHM)

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5. Auto Titrator(T5, METTLER TOLEDO)

6. Infra Red Spectroscopy (Perkin Elmer, Spectrum Two)

7. Muffle Furnace (ALLY ONE)

8. pH Meter

9. Tapped Density Apparatus (ELECTROLAB)

10. THIN Layer Chromatography

11. HPLC (ALLIANCE e2695, Empower soft.)

12. Melting Point Apparatus (LABINDIA)

13. Particle Size Analyzer (MALVERN MASTERISIZER 2000)

14. Viscometer (BrookfieldDV2T)

15. Refractometer (ANTON PAAR Abbemat 500)

16. Inductive Coupled Plasma (PERKIN ELMER Optima 8300)

17. Hot Air Oven (NEWTRONIC)

LIST OF GENERAL APPARATUS IN Q.C. LAB

1.Burette 2.Pipette 3.Conical Flask

4.Beaker 5.Glass Bowl 6.Measuring

Cylinder

7.Separating 8.Crucible 9.Nestler

Funnel Cylinder

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10.Distillation 11.Round Bottom Flask 12.Standard

Apparatus Flask

13.Iodine Flask 14.Centrifuge tube 15.Specific

Gravity Bottle

16.Condensors 17.Petri dish 18.Dessicator

19. Watch Glass 20. Heating Mantel 21. Bunsen

Flame

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Tablet section Weight Variation Test:-

BY USING DIGITAL BALANCE (ELECTROLAFig –
digital balance

PROCEDURE:
Make sure that the balance is kept clean. Ensure that the
calibration status is valid. Ensure that spirit level is in the
center of the circle. Connect the power cable to the mains
and switch „ON‟. Automatically self-checking starts from “che-3” & ends with OFF. Press
ON/OFF key, all the display will glow. Press TARE KEY 0.00000 marks appear on the
display. The stability of the reading is obtained which is indicated by an arrow mark on the
left side of the display. Once the stability is attained, the balance is ready for weighing. Place
the material to be weighed on the pan & note down the reading after the arrow mark appears
on the left side of the display. After completion of weighing press, “ON/OFF” key.

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“STAND BY” light glows. Clean the balance immediately after weighing.

PRECAUTIONS:
Do not weigh on the pan directly. Always use butter paper.
Do not place heavy glassware on the pan. It may damage the instrument Do
not weigh corrosive acids & hot materials.
Do not shift the balance once positioned.
Do not give shock to pan or table.
Close the glass doors on the sides and top before recording the weights handle the balance
gently and carefully.
Do not press the material on the pan with spatula
Test Procedure
Weigh individually 20 units selected at random and calculate the average weight. Not more
than two of the individual weights deviates from the average weight by more than the
percentage given in the pharmacopeia and none deviates by more than twice that
percentage.IP/BP & USP limits for tablet weight variation is given below.

IP/BP Limit USP

80 mg or less ± 10% 130mg or less

More than 80mg or Less ± 7.5% 130mg to 324mg

than 250mg
250mg or more ± 5% More than 324mg

2 .SIZE OF TABLET :- Size of tablet is measure with the help of VERINERCALLIPER

3. HARDNESS TEST

Tablet requires a certain amount of strength or hardness to with stand mechanical shock of
handling in manufacturing, packaging and shipping.

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Fig -Hardness tester

FRIABLITY TEST

Friability (the condition of being Friable) testing is a method, which is employed to determine
physical strength of uncoated tablets upon exposure to mechanical shock and
attrition

FIG:- FIABILTY APPARTUS (ELECTROLAB)

PERCENTAGE FRIABLITY LESS THEN 1%

DISINTEGRATION TEST

These test is provide to determine whether uncoated or coated tablet disintegrate within a
prescribe time when placed in liquid medium under the prescribed experimental condition

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Apparatus

For tablets and capsules of normal size The apparatus consists of a basket-rack assembly, a
1litre beaker, a thermostatic arrangement for heating the fluid and a mechanical device for
raising and lowering the basket in the immersion fluid at a constant frequency rate.
Basket-rack assembly- The basket-rack assembly is rigid and supports six cylindrical glass
tubes, 77.5 ± 2.5 mm long, 21.5 mm in internal diameter and with a wall thickness of about 2
mm (Fig. 2.5.1-1). The tubes are held vertically by two superimposed transparent plastic
plates, 90 ± 2 mm in diameter and 6.75 ± 1.75 mm thick perforated by six holes having the
same diameter as the tubes. The holes are equidistant from the centre of the plate and are
equally spaced from one another. Attached to the underside of the lower plate is a woven
stainless steel wire cloth with a plain square weave with 2.0 ± 0.2 mm mesh apertures and
with a wire diameter of 0.615 ± 0.045 mm. The upper plate is covered with a stainless steel
disc perforated by six holes, each about 24 ± 2 mm in diameter, which fits over the tubes and
holds them between the plastic plates. The holes coincide with those of the upper plastic plate
and the upper open ends of the glass tubes. A suitable means is provided to suspend the
basket-rack assembly from the raising and lowering device using a point on its axis

The plates are held rigidly in position and 77.5 mm apart by vertical metal rods at the
periphery and a metal rod is also fixed to the centre of the upper plate to enable the assembly
to be attached to the device for raising and lowering it smoothly at a constant frequency of
between 28 and 32 cycles per minute through a distance of 50 to 60 mm. The time required
for the upward stroke is equal to the time required for the downward stroke, and the change in
stroke direction should be smooth and not abrupt. There should be no appreciable horizontal
motion or movement of the axis from the vertical. The design of the basket-rack assembly
may be somewhat different provided specifications for the glass tubes and the screen mesh
size are unchanged. Discs A cylindrical disc for each tube, each 20.7 ± 0.15 mm thick in
diameter and 9.5 ± 0.15 mm thick, made of transparent plastic with a relative density of 1.18
to 1.20, and pierced with five holes, each 2 mm in diameter, one in the centre and the other
four spaced equally on a circle of radius 6 mm from the centre of the disc. Four equally
spaced grooves are cut in the lateral surface of the disc in such a way that at the upper surface
of the disc they are 9.5 mm wide and 2.55 mm deep and at the lower surface 1.6 mm.
Medium. The assembly is suspended in the liquid medium in a suitable vessel, preferably a
1litre beaker. The volume of liquid is such that the wire mesh at its highest point is at least 25
mm below the surface of the liquid, and at its lower point is at least 25 mm above the bottom

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of the beaker. At no time should the top of the basket rack assembly become submerged.
There is a thermostatic arrangement for heating the liquid and maintaining the temperature at
37º ± 2º.

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Fig :-disintegration apparatus Procedure

• Uncoated and Plain Coated Tablets

• assemble the apparatus when the device for raising and lowering the basket-rack
assembly is at rest and its cylinder is in the extreme down position;
• with 2.5 L of water in the cylindrical jar, adjust the apparatus until the level of fluid in
the jar coincides approximately with the mid-line of the upper plastic plate (see Figure
II);
• maintain the temperature of the fluid at 37 ± 2oC by a suitable means
• remove the basket-rack assembly from the water and disassemble;
• select at random six tablets from the sample and place one in each of the tubes of the
basket-rack assembly;
• place a plastic or glass disk on each tablet tube
• , re-insert the assembly in the water and set the machine in motion;
• the plastic or glass disks should travel up and down freely, exerting a gentle rubbing
action on each tablet;
• notes the time taken by six tablet for complete conversion into small particle
• uncoated tablets pass the test if each of the six uncoated tablets disintegrates3in not
more that 15 minutes;
• Plastic coated tablets pass the test if each of the six plain coated tablets disintegrates
in not more than 60 minutes. If any of the tablets has not disintegrated at the end of 60
minutes, repeat the test on a further six plain coated tablets, replacing the water in the
cylindrical jar with Hydrochloric Acid Solution (0.1 M). The tablets pass the test if
each of the six tablets disintegrates within 60 minutes in this acid medium.

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For enteric coated tablet 0.1m hydrochloric acid

Put one tablet into each tube suspend the assembly in the beaker contain 0.1M Hcl and
operate without the disc for 2hour

Remove the assembly from liquid

No tablet show sign of crack that would allow escape of content or disintegration apart from
fragment of coating

Phosphate buffer pH6.8

Replace the liquid in the beaker with mixed phosphate buffer pH 6.8

Add a disc to each tube and operate the apparatus for further 60 minutes

The tablets pass the test if all six tablets disintegrated

7. High performance liquid chromatography

It is a technique in analytical chemistry used to separate, identify, and quantify each

component in a mixture is a technique in analytical chemistry used to separate, identify, and
quantify each component in a mixture.

FIG:- High performance liquid chromatography

Principal- it the based on principle of adsorbance

Component of HPLC :

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Pump- The role of the pump is to propel (force) a liquid (the mobile phase) through the
chromatograph at a specific flow rate, expressed in ml/min. flow rates in HPLC are 1-2
ml/min and typical pumps can reach pressures in the range of 2000 – 9000 psi but in
applications covered under UHPLC mode operating pressure can be as high as 15000-18000
psi The normal flow rate stability must be < 1%.

An ideal pump should have the following characteristics:

• Solvent compatibility and resistance to corrosion

• Constant flow delivery independent of back pressure

• Low dead volume for minimum problems on solvent changeover

The main types of pumps used in HPLC (or in LC) are the following

Constant Pressure Pumps: Provide consistent continuous flow rate through the column with
the use of pressure from a gas cylinder.

Constant Flow Pumps: a) Reciprocating Piston pumps deliver solvents through

reciprocating motion of a piston in a hydraulic chamber. The main drawback of a
reciprocating pump is that it produces a pulsing flow. With a flow-sensitive detector, such as
micro-adsorption detector, a pulse damping system must be used and detector sensitivity is
reduced.
b) Syringe type pumps are suitable for small bore columns. Constant flow rate is delivered to
column by a motorized screw arrangement.

The pump should be inert to solvents, buffer salts and solutes. They are made of stainless
steel, titanium and resistant minerals.

There are two types of pump operation:

• Isocratic pump - delivers constant mobile phase composition

• Gradient pump – delivers variable mobile phase composition

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INJECTOR

The sample should be introduced as a plug, without disturbing the column packing. The
injector serves to introduce the liquid sample into the flow stream of the mobile phase.
Typical sample volumes are 5-20 μL. The

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injector must be able to withstand the high pressure of the mobile phase. A precolumn, a
small removable section of tubing containing the same packing material as the column, can
be used ahead of the analytical column to protect the latter from contamination. The
precolumn also acts as a buffer to prevent channeling of the packing during injection.

Column

The column is considered the heart of the chromatograph. The success or failure of a
particular analysis depends on the choice of column. The column‟s stationary phase separates
the sample components using various physical and chemical parameters.

There are four types of columns used in HPLC:

• High performance analytical columns [internal diameter (i.d.) 1.0-4.6 mm; lengths 15
–250 mm] - used mainly for qualitative and quantitative analysis
• Preparative columns (i.d.> 4.6 mm; lengths 50 –250 mm) – used mainly for
preparative work
• Capillary columns (i.d. 0.1 -1.0 mm; various lengths)
• Nano columns (i.d.< 0.1 mm)

The tubing used for the construction of columns can be:

• Glass – mostly for Biomolecules

• Stainless steel – the most popular; can withstand high pressures

• PEEK polymer – chemically inert to most solvents and biocompatible

Columns are packed with small diameter porous particles. Usually the size of the porous
materials used are 1,6 – 5 μm. The column pickings used in liquid/solid chromatography (LC,
HPLC) are silica gel, charcoal and alumina. Most users particles in the column usually have a
chemically bonded phase on their surface which interacts with the sample components to
separate them from one another – for example, C18 is a popular bonded phase. The process
of retention of the sample components is determined by the choice of column packing and the
selection of the mobile phase to push the analytes through the packed column.

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INHALER DEPARTMENT

Inhalers: - An inhaler (or puffer) is a medical device used for delivering medication into the
body via the lungs. It is mainly used in the treatment of asthma and chronic obstructive
pulmonary disease.

Metered-dose (MDI):-

Two DPIs of the Turbohaler type, displaying no. of doses remaining (house key for scale)

The most common type of inhaler is the pressurized metered-dose inhaler(MDI). In MDIs,
medication is typically stored in solution in a pressurized canister that contains a propellant,
although it may also be a suspension. The MDI canister is attached to a plastic, hand-operated
actuator. On activation, the metered-dose inhaler releases a fixed dose of medication in
aerosol form. The correct procedure for using an MDI is to first fully exhale, place the
mouth-piece of the device into the mouth, and having just started to inhale at a moderate rate,
depress the canister to release the medicine. The aerosolized medication is drawn into the
lungs by continuing to inhale deeply before holding the breath for 10 seconds to allow the
aerosol to settle onto the walls of the bronchitis and other airways of the lung. Some inhalers
are made to act instantly in case of an asthma attack, and others are made to act later.

Dry Powder inhalers release a metered or device-measured dose of powdered medication

that is inhaled through a DPI device.

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Nasal

Nasal inhalers contain decongestant drugs to relieve congestion in the upper respiratory tract.
The active ingredient in most decongestants is either pseudoephedrineor phenylephrine.
Many are solution over the counter without a prescription.

APPARATUS USED FOR QUALITY CONTROL:

Conductivity meter: conductivity meters and sensors combine high accuracy and precision
with ease of use and low maintenance. Truly the right choice for a wide range of applications
for both in-line and off-line measurements.

FIG:-Conductivity meter

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FIG:-Melting point

Automated Melting Point Apparatus:-

Opti Melt provides a fast and accurate means of automatically determining the melting points
and melting ranges of chemical substances. With microprocessor-controlled temperature
ramping, a built-in digital camera, and a selling price that is half that of competing models,
OptiMelt offers the best value of any commercially available melting point apparatus.

Automated Measurements:-OptiMelt is specifically designed for unattended operation. It

has a built-in digital camera that continuously captures real-time images of the samples, and it
uses digital image processing to determine results. The melting points and melting ranges are
prominently displayed on the front panel and automatically recorded into memory for later
review.

Fast Measurements

The small, aluminum oven design, along with microprocessor-controlled temperature

ramping, provides fast and repeatable warm-up and cool-down cycling. Programmable ramp
rates from 0.1 ºC/min to 20 ºC/min, in 0.1 ºC/min increments, provide measurement
flexibility.

Accurate Results

OptiMelt uses a platinum RTD sensor and makes temperature measurements to 400 °C with
0.1°C resolution. It is easily calibrated in the field against certified reference standards and

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complies with modern Pharmacopeia protocols. The instrument remembers the date of the
last calibration which is included in all reports.

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Digital Image Processing

The OptiMelt system is unique among melting point analyzers. It has a built-in,
highresolution digital camera to capture real-time images of the samples. It then uses digital
image processing to determine phase transitions in the samples.

Conclusion: Tablets are the solid dosage form. It is administrated by oral route. Ointments,
creams &lotions are semi solid dosage form .It is topical preparation. It is used external. It is
used in medicament. Testing is necessary for pharmaceutical manufacturers to develop a
given drug entity in a new and improved good bioavailability & quality of manufacturing
product.

1. QUALITY ASSURANCE (QA)

QA is a way of preventing mistakes or defects in the manufactured products and avoiding

problems when delivering solutions, services to customers; which ISO 9000 defines as “part
of quality management focused on providing confidence that quality requirements will be
filled”. It can be obtained by presenting suitable standard operating procedures(SOPs) in
house

Various Departments of Quality Assurance

DOCUMENTATION: Documentation is an integral part of good manufacturing practices.It

defines a system of information and control so that risks so inherent in misinterpretation
and /or error in oral communication are minimized.

Types of Documents:

1. Batch Related Documents: BMR, BPR

2. Non –Batch Related Documents: check list, protocols
2. VALIDATION: It is a process of establishing documentary evidence
demonstrating that a procedure, process, or activity carried out in production
testing maintains the desired level of compliance at all stages. In pharma
industry, it is very important apart from final testing and compliance of

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product with standard that the process adapted to produce its self must assure
that process will consistently produce the expected results.

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The field of validation is divided into a no of sub sections including the following

1. Equipment Validation
2. Process validation
3. Cleaning validation
4. Analytical method validation
5. Revalidation

1. PRODUCTS MANUFACTURED IN CHIROS PHARMA

Pencillin and Cephalosporin oralsolid dosage forms which includes stable clavulanic acid is
manufactured in both 1 and 2 units .

Unit 1 products (cephalosporin):-

1. Cefixime 50, 100 mg DT Tablets

2. Cefixime 200 mg Film Coated Tablets
3. Cefixime 100,200 mg+ ofloxacin 100, 200 mg tablets
4. Cefiime 100, 200 mg+ Azithromycin 125, 250, 500 mg tablets
5. Cefixime 50,100 mg Dry Syrup
6. Cefixime 100, 200 mg + Potassium Clavulanate 62.5, 125 mg tablets
7. Cefpodoxime Proxetil 50, 100 mg DT Tablets
8. Cefpodoxime Proxetil 200 mg tablets
9. Cefpodoxime Proxetil 50, 100 mg Dry Syrup
10. Cefpodoxime Proxetil 100, 200 mg +Potassium Clavulanate62.5, 125 mg tablets
11. Cefpodoxime Proxetil 200 mg + Ofloxacin 200 mg tablets
12. Cefuroxime Axetil 125 mg DT Tablets
13. Cefuroxime Axetil 250, 500 mg Film coated Tablets
14. Cfeuroxime Axetil 125 mg Dry Syrup
15. Cefuroxime Axetil 250, 500 mg + Potassium Clavulanate 125 mg Tablets
16. Cefdnir 300mg Tablets
17. Cefdnir Oral Suspension 125 mg Dry Syrup
18. Cephalexin 250, 500 mg capsules

Unit 2 products (pencillin):-

1.Amoxicillin trihydrate 125, 250 mg DT Tablets

2.Amoxycillin trihydrate500 mg Tablets
3.Amoxicillin trihydrate 250, 500 mg Capsules
4.Amoxicillin trihydrate 250 mg+ Dicloxacillin Sodium 250 mg Capsules
5.Amoxicillin trihydrate 250, 500, 875 mg + Potassium Clavulanate 125 mg Tablets

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6.Amoxycillin 125 mg Dry Syrup

7.Amoxicillin trihydrate 125, 200, 400 mg + Potassium Clavulanate 28.5, 31.25, 25.57 mg
Dry Syrup
8.Amoxicillin trihydrate 200 mg+ Potassium Clavulanate 28.5 mg DT Tablets
9.Ampicillin 125, 250 DT Tablets
10.Ampicillin 250, 500 mg Capsules
11. Ampicillin 125 mg/5ml Dry Syrup
12. Ampicillin 250 mg+ Dicloxacillin Sodium 250mg Capsules
13. Ampicillin 250mg+ Cloxacillin 250mg Capsules
14. Sultamicillin Tosilate Dihydrate 250mg ( Ampicillin 220, 440mg + Sulbactum 147, 294
mg) Tablets
15. sultamicillin Tosilate Dihydrate 375, 750 mg (Ampicillin 147 mg+ Sulbactun 147 mg)
Dry Syrup
16. Flucloxacillin 250, 500 mg Capsules
17. Phenoxymethylpencillin oral Suspension 125, 250 mg
18. Phenoxymethylpencillin 250, 500 mg Tablets

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CONCLUSION

Industrial plant plays a vital role in any industry. Quality product ensures the company’s
prospects in order to create loyalty.Cipla pharmaceuticals are no longer beyond the
objective to provide quality product for the target customer but to gain the multi-national
infrastructure.

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