An Industrial Training Report

at
S.R. DRUG LABORATORIES Pvt. LTD.

SATUNGAL, KATHMANDU,NEPAL

From 21 june 2023 to 20 july 2023

Submitted By Submitted To

Name of the student: RAJIP NEPAL Supervisor: MR.VISHAL KAJLA

Class: 7TH semester Designation: Assistant Professor,
Roll No: 20-B-Pharm-175 Department of Pharmacology
Batch: 2020-2021

College of Pharmacy
RIMT University, Mandi Gobindgarh, Punjab (2020-21)

Year (2023)
 Acknowledgement
The sequence for acknowledgement should be as follows:

1. I would like to express my great appreciation to Sh. Hukum Chand Bansal (Chairman of
the University)
2. I would like to offer my special thanks to Dr. B.S.Bhatia (Pro Vice Chancellor, RIMT
University), Mr. Rakesh Mohan (Registrar, RIMT University) & Dr. M.S. Bindra (Director
academics, RIMT University)
3. Advice given by Dr. Sanjiv Mittal (Director, School of pharmaceutical Sciences) & Dr.
Ajay Bilandi (Principal, College of Pharmacy) has been a great help during my whole
training.
4. I am particularly grateful for the assistance provided by Factory Manager, Mr. Binod Kumar
Gupta,
(S.R. drug and laboratories Pvt.Ltd).
5. I wish to acknowledge the help provided by -------------------- (Any teacher name/mentor/ or
any other teacher)
6. My special thanks are extended to the whole staff and my friends for the accomplishment
of this training.

RAJIP NEPAL
Industrial training Certificate
 Table of contents
Sr. no Title Page No.
1. Introduction 1-2
2. Classification of departments 2
3. Tablet Section 3-14
4. Capsule section 14-18
5. Dry syrup section 18-19
6. Liquid section 19-22
7. Ointment section 22-23
8. ORS section 24
9. External preparation Section 24-25
10. Packaging section 25-29
11. Over printing section 29-30
12. Production change over 30
13. Store 30-32
14. Quality control department section 33-35
15. Microbiological section 35-37
16. Quality Assurance section 37-39
17. Maintenance 39-41
18. Brand of Marketed formulation 42
19 Conclusion 43
LAYOUT OF INDUSTRIAL

5
 PREFACE

Pharmacy is a profession which is concerned with the art and science of preparing suitable and convenient
material for distribution and use in the treatment and prevention of diseases, so it is a fully technical
profession where practical knowledge and important along with theoretical knowledge. I am presenting a
report on In-plant training at SR Drug Laboratory Pvt. Ltd.

In this report, I have elaborated information relating to pharmaceutical products, machinery information,
documentation, management procedures & all my personal gained information.

This report contain information about resources management, production of pharmaceutical goods, method
of production, formulation and research related activity, documentation system, water supply system and
utility & maintenance and instruments.

6
 List Of Figures:
S.N Figures

1 Rapid Mixing Grandulator

2 Oscilating Grandulator

3 Multi-Mill

4 Fluidized Bed Drayer

5 Double Side Rotary Tablet Press Machine

6 Automatic Coating Machine

7 Flowchart Of Tablet Manufacturing By Wet Granulation Process

8 Mixing Tank With Heating Jacket & Strirrer

9 Colloid Mill

10 Ointment Manufacturing Plant

11 Filing

12 Manufacturing Tank

13 Automatic Liquid Bottle Filling Machine

14 Strip Packing Machine

15 Air Handling Unit

7
 OBJECTIVES

General Objective:
The general objective is to experience the real working conditions of the pharmaceutical industry and study
the organization and functioning of a pharmaceutical company.

Specific Objectives:
1. To familiarize ourselves with the manufacturing processes of pharmaceutical products in the
factory.
2. To develop managerial skills in different sections of a pharmaceutical company.
3. To understand the sequence of procurement, processing, production, handling documentation, and
quality assurance throughout the various steps from raw materials to end products.
4. To become familiar with the equipment and instruments used in drug manufacturing within the
pharmaceutical industry.
5. To learn about the processes of quality control and in-process control of raw materials and finished
products.
6. To gain insight into the design and construction of pharmaceutical industry buildings.
7. To acquire knowledge about documentation, validation, good manufacturing practices (GMP), and
other related processes.

8
 SR Drug Laboratory Pvt. Ltd

Introduction

SR Drug Laboratory Private limited, a national pharmaceutical company synonymous with high product
quality was established in June 12 th 2003 (2059 B.S) with the objective of producing highest quality drugs
for better health care of the patients and has started commercial production from September 2004 (2060
B.S) with 86 different products. In a short span of 4 years, SR has carved a niche for itself among the
Nepalese pharmaceuticals. Within a short period of time, it has expanded its products to 176 and is rated as
one of the promising pharmaceuticals of Nepal.

SR is located at Satungal, Kathmandu, and its Corporate Office is at Tripureshwor. SR has a team of
competent management and technical professionals and a group of dedicated members at all levels who
have been working together as a team to create an outstanding record of success and growth in the Nepalese
pharmaceutical Industry. It has latest technology adopted Production Plant & sophisticated QC lab and fully
incorporates all the necessary measures for the quality drug production. Due to its continuous improvement
in Product, Process, System & Quality Performance, it was awarded with WHO-GMP in May 16th 2006
and ISO 9001: 2000 in 15 th May 2006. With the motto ''Care for the environment, environment will care
you'', SR has been implementing Good Environmental Management System for which it was awarded with
ISO 14001: 2004 in September 7th 2006.

SR is committed to implement and maintain WHO-GMP norms at every stage from Procurement,
Manufacture, Packaging, and Storage to Sales & Distribution. It produces a wide range of products which
includes tablets, capsules, syrup, suspensions, dry syrup and Ointment in the market and in near future also
it plans to launch many useful healthcare products.

Products of S.R.

At present, SR is manufacturing a number of drugs from various therapeutic categories in different dosage
forms. The therapeutic categories of drugs and different dosage forms being manufactured in SR are given
below:-

1
Therapeutic categories:

 Gastro-intestinal
 Anti-inflammatory
 Anti-Allergic
 Nutritional Supplement
 Antimicrobials
 Cardio-Vascular
 Antidiabetics
 Anxiolytic & Psychotropic

Dosage Forms:

 Tablets
 Capsules
 Dry syrup
 Syrup
 Ointment
 External preparations (lotions, sanitizers)
 ORS
 drops

Departments of SR
 Production
 Quality control
 Quality Assurance
 Store
 Secondary Packaging
 Maintenance
 R and D
Production Department
Production department of SR is large as it is engaged in manufacturing of more than 180 products. There
are two areas inside the production section. They are grey area and black area. The manufacturing
activity is carried out in the grey area whereas labelling and secondary packaging is done in black area.
Grey Area and is maintained under class 1,00,000 i.e number of particles of size less than 0.5 micron
should not exceed 1,00000 per cubic feet. The corridor is maintained with positive pressure and the
processing unit with the negative pressure so as to control cross contamination as the dust may be
generated in the production area. Corridor must be positive of 15 Pascal than that of the room. The walls
of the processing area are plastered to smoothness and painted with epoxy coating. The ceiling in the
manufacturing area is false ceiling and painted with epoxy paint. The covings in the manufacturing

2
 area are provided with epoxy paint. All electrical fixtures in the process area are flushed with the
wall and false ceiling. Standard Magnehelic pressure Gauge is installed in every door to monitor
the pressuredifference.

Production is carried out as per BMR and instruments are used as per clearly written SOPs.
Production department has been divided into:

 Non-penicillin section (tablets, capsules, liquids, syrups, ointments, drops)

 Penicillin section
 Cephalosporin section
 ORS section
 External preparation section (sanitizers, lotions etc.)
 Packaging section

Tablet Section
Tablets are the oral unit solid dosage form that covers at least 90% of all dosage forms used to
provide systemic administration of therapeutic agents. Tablets are popular among manufacturer
and patients dueto

 Convenient and safe way drug administration

 Compared to other dosage form, tablets have general advantages in terms of the
chemical,physical and microbiological stability.
 convenient to handle and can be prepared in a versatile way.
 Preparation procedure enables accurate dosing of the drug.
 Can be relatively cheaply mass produced, with robust and quality-controlled
productionprocedures giving an elegant preparation of consistent quality.

Tablet section of SR produces different coated, uncoated, chewable and dispersible tabs of oblong
and round shape and size of 5, 6.3, 8, 10, 12.7, 16, 19 mm diameter as per the respective
formulation record.

Tablet manufacturing consists of following sections:

 Air lock
 Dispensing booth
 Granulation room
 Tablet compression room
 Tablet inspection room
 Coating room
 Quarantine room

3
EVALUATION PARAMETERS USED IN TABLET SECTION:

In tablet manufacturing, various evaluation parameters are assessed to ensure the quality and consistency
of tablet products. Here are some key evaluation parameters:

1. Weight Variation: Tablets are weighed individually, and their weights should fall within a
specified range to ensure uniformity.

2. Thickness: Tablet thickness is measured to ensure consistency in size and shape.

3. Hardness: Tablet hardness or crushing strength is tested to determine its ability to withstand
handling and transport without breaking.

4. Friability: This test assesses the tablet's resistance to abrasion during handling and packaging. It
measures the percentage weight loss of tablets after a specified number of rotations.

5. Disintegration: The time it takes for a tablet to disintegrate into small particles in a simulated
stomach environment is monitored. It ensures the tablet will release its active ingredients in a
timely manner.

6. Dissolution: Dissolution testing evaluates how well a tablet dissolves in a simulated

gastrointestinal fluid. It assesses the availability of the active ingredient for absorption by the
body.

7. Tablet Identification: Tablets should be clearly marked with relevant information, such as product
name, dosage strength, and manufacturer details.

8. Visual Inspection: Tablets are visually inspected for defects, including chipping, cracking, and
discoloration.

9. Friability: Tablets are subjected to mechanical stress to assess their resistance to chipping or
breaking during handling and transportation.

10. In-process Control: Various parameters are monitored during the tablet manufacturing process to
ensure that tablets meet quality standards at each stage of production.

11. These parameters help pharmaceutical companies ensure the quality, safety, and efficacy of tablet
products, and they are essential for regulatory compliance and consumer safety.

4
Air Lock
Air lock is an enclosed space with two or more doors, which is interposed between two or more rooms
for controlling the airflow between the rooms. An airlock is designed for and used by either people or
goods.

Dispensing Booth

Dispensing booth is the area designed to dispense the starting materials for production and sampling of
raw materials by quality control. It is a white area i.e. class 100 and is designed in such a way as to
minimize cross-contamination and to produce maximum safety to the workers. The dispensing and
sampling procedure is carried out in presence of a QC personnel and a production officer. Equipment
used in dispensing booth includes:

 Dispensing booth (Reverse flow – Air Pac)

 Electronic balance (Shimadzu)
 Weighing balance (Metler- Toledo)
Granulation Room
Granulation is the process in which dry primary powder particles are processed to adhere to form larger
multi-particle entities called granules. Pharmaceutical granules typically have a size range between 0.2
and 4.0 mm, depending on the subsequent use of the granules.

Reasons for granulation

 To prevent segregation of the constituents of the powder mix

 To improve the flow properties of the mix

 To improve the compaction characteristics of the mix.

SR makes use of following methods of granulation

1. Direct compression where the sieved raw materials after blending are directly compressed.

2. Wet granulation where the sieved raw materials are converted into uniform granules by mixing the
powder with granulating fluid | binding sol n which are then compressed.

5
 Equipments Used For Granulation, Mixing And Drying

Fig.1 RAPID MIXING GRANULATOR FIG.2 OSCILLATING GRANULATOR

FIG.3 MULTI-MILL FIG.4 FLUIDIZED BED DRAYER

 Vibro shifter (Indo German Pharma Machinery)

 Multi-mill (Chamunda Pharma Machinery)
 Oscillating Granulator (Chamunda Pharma Machinery)
 Rapid Mixer Granulator (Sams Machine Tools)
 Fluidized Bed Drier
 Heating vessel (kettle)
 Sieve
 Electronic balance (wild cat)
 Tray drier (Aastha International)
 Mass mixer

6
 Process For Granulation, Mixing And Drying

Dispensed RM are first brought to the Mixing, granulating and drying room with the help of a trolley
where RM are divided for mixing, lubrication, paste making purpose. The processing steps are:

 Sieving of RM in Vibro-shifter using different mess (60, 40, 24) for obtaining uniform particle size.
 Mixing in RMG at slow speed using only impellers (without chopper) for the specified time (about
30 mins). Prolonged mixing would result in demixing.
 Starch paste preparation
 e.g 1 kg starch is added, in 2 ltr. of DMW heated to 70ºC with constant stirring.
 Then 12 ltr. boiled DMW (95º-100ºC) is added and stirred properly. This cooked starch is in the
form of thick paste. If thin paste is required, further 4 lts DMW (50º C) is added. Paste is cooled to
45º- 50º C.
 Usually for tablets of size 5-10mm, thick starch paste is desirable
 And for tabs of size 10-19mm, thin starch paste is desirable.
 Binding solution preparation It is prepared by dissolving Polyvinyl Pyrrolidone in DM water
heated to 40º C. Thus, prepared PVP solution is then added to Starch paste and cooled to 50º C.
 Wet Granulation
 Binding solution is transferred to mixture of step 2 in RMG and kneaded for 5 min without chopper
(with chopper for 2 min)
 Granulating current adjustment is critical in RMG
For small tablets size: 5-8 mm - 7 Amp

For large tablets size: 10- 19 mm -9 Amp

 Shredding by passing wet mass through Oscillating Granulator or Multimill with hole diameter
6mm which chops wet granules into smaller size so that drying is uniform and less time consuming.
 Drying in FBD for specified time (30-40 mins)
 Inlet air adjusted to temp of 55º C and outlet air to 45ºC
 Drying time depends on the nature of the drug. For drugs like Metformin, Paracetamol,
Metronidazole, Tinidazole, Paracetamol + Chlorpheniramine (Coldarest) little moisture should be
retained while drying for compression to occur; otherwise, friability will be failed.
 Rasping in Oscillating Granulator or Multimill using hole of 2mm diameter to make granules of
uniform size.

7
Air lock- Blending room

 Cone blender (120 Kg capacity)

 Octagonal blender
 Cone blender

Process
Sieved lubricants and dried granules are fed into octagonal/ cone blender and mixed for specified time
which is usually around 45 min.

Tablet Compression Room

The dominating technique of forming tablets is by powder compression, i.e. forcing the particles into close
proximity to each other by confined compression. This enables the particles to cohere into porous, solid
specimen of defined geometry. The compression takes place in a die by the action of two punches, the
lower and the upper, by which the compressive force is applied. Compression of the tablet is done by the

Rotary compression machine in controlled temperature (25±2oC) and relative humidity (45±5 %).

Technical Problems Arised During Tableting

 weight and dose variation of the tablets

 Low mechanical strength of the tablets
 Capping and lamination
 Adhesion or sticking of powder material to punch tips
 High friction during tablet ejection

Various instruments available in the compression room are:

 16 Station compression machine (CPMD-3 Chamunda)

 27 Station Double Rotary Compression Machine (GMP square model Type-CPMD3) with De-dust
 Electronic balance
 De-humidifier
 Hygrometer

8
 Fig. 5 DOUBLE SIDE ROTARY TABLET PRESS MACHINE

Parts of Tablet Compression Machine:

 Hopper: It is used for holding and feeding granules to be compressed.

 Dies: It defines the size and shape of the tablet.

 Punches: It is used for compressing the granulation within the dies.

 Feed frame: it is used for moving the granulation from the hopper to the dies.

 Upper and lower cam track: It is used for guiding the movement of the dies and
punches.↓
 Mounting frame

 Upper roller and lower roller

 Chute: It is used for the discharge of the compressed tablets.

Things That Should Be Considered During Compression Are

 1-2 mm gap should be kept between Turret and Feed frame to avoid friction and maintain proper
spread of granules within feed frame compartments.
 Weight and Hardness Adjustment- weight is adjusted first followed by hardness. Hardness should
be adjusted in such a way that tab should pass Friability (NMT 1%) and DT (NMT 15 min for
uncoated tabs) but at the same time tabs should be of desired thickness because variation in thickness
can cause problem during packing. Wt. variation, Hardness and DT should be checked every half
hourly or so by the operator and IPC to adjust variation if it has occurred.

9
In-Process Quality Control

The objective of In-Process control is to prevent the production of substandard drug product from
occurring by early detection of deviation. Control is executed by sampling, inspection and testing of the
drug product at certain phases of the production process.

Responsibilities of IPQC

 Analysis of in process sample as per in house specifications

 Sampling of Intermediate product, bulk product, and finished product as per SOPs and sending
them to QC department for analysis
 Check the material dispensed are of mentioned AR no, quantity and within the shelf life
 Provide line clearance for production of every dosage form

Equipments used in IPQC

 Tablet Disintegration Test Machine (Campbell Electronics)

 Friability Test Apparatus
 pH meter
 Hardness Tester
 Vernier Calliper
 Electronic balance-2 (Shimadzu)
 Moisture balance

Tablet Inspection Room

After the completion of tablet compression, tablets are inspected using tablet inspection machine or
manually. Both sides of tablets are observed under tablet inspection machine to remove damaged tablets
and tablets containing unwanted particles like black particles.

Equipments
 Tablet inspection belt (Campbell electronics)

10
 Coating Room
Compresses tablets are coated in the coating room. Coating is a process by which an essentially dry, outer
layer of coating material is applied to the surface of the dosage form in order to confer specific benefits
that broadly range from facilitating product identification to modifying drug release from the dosage form.
Coating can be film coating, sugar coating and enteric coating. Film coating and the enteric coating are the
two main coating processes followed in the SR.

FIG.6 AUTOMATIC COATING MACHINE

Film coating – Increase tab wt. by 2-5 %

 Prevent the drug from external environment particularly moisture. (Ranitidine)

 Mask bitter taste of drug (Metronidazole)
 Provide elegance.
 Easy identification.
Enteric Coating – Increase tab wt. by 9-10 %

 To prevent acid labile drug from gastric fluid

 To prevent gastric irritation
 To deliver drugs intended for local action in intestine
 To deliver drugs with high bioavailability in basic medium to their primary absorption site i.e.
intestine
Preparation Of Coating Solution

Film coating solution:

 1kg of coating material is added in 8-10 ltr. of DMW heated to 60ºC.

 The solution is left for overnight
 Composition of the coating formulation:
11
 o HPMC - Polymer (film former)
o PEG - Plasticizer
o Benzyl alcohol - Antimicrobial
o Titanium Dioxide- Opaquant

Enteric coating solution:

 1 kg of coating material is added to 4 ltr. of DMW heated to 60ºC.

 The solution thus prepared is ready for coating
 Instacoat is used for enteric coating

Coating solution is milled in colloid mill before coating to ensure proper dispersion and particle size
reduction. Otherwise, coating solution gets blocked in Spray Gun.

Coating Room

Coating Room at SR consists of:

 Coating pan (3) of size 12'', 24'', 36''.

 Spray Gun for spraying coating solution which works on the principle of compressed air sent
through Air Compressor.
 Hot air Blower is adjusted to required temp to facilitate effective drying.
 Dust extractor is fitted properly so that dusts produced during coating are carried away.

Requirements for Coating

Kernels are prewarmed at 40ºC for about 15 min

Angle of pan = 45 º

Temp of Hot air = 60º- 80ºC

RPM of Coating Pan = 10-12

Compressed Air Pressure for Spray Gun Bullows = 1- 1.5 kg/cm2

Spray rate = about 1.5 liter. /hour

12
Quarantine Room
Quarantine is the status of starting or packaging materials, intermediates, bulk or finished products
isolated physically or by other effective means while a decision is awaited on their release, rejection
or reprocessing.

Tablet Manufacturing Process:

Raw material

QC analysis

QC release

Raw material requisition → RM dispensing ← supervised by QA

Sieving

Dry mixing in mass mixture

Making binding solution

Granulation in mass mixture

Shredding in OG

Drying in FBD

Rasping in OG

13
 Lubrication in double cone blender

QC release

Compression

Coating

QC release

Sorting

Packing

QC release

QA release

Store

Fig.7: Flow chart of Tablet Manufacturing by Wet Granulation Process

Capsule Section

Capsules are solid unit dosage form of medicament(s) in which the drug is enclosed in a practically
tasteless, hard or soft soluble container or shell made up of a suitable form of gelatin.

14
Steps of capsule production

 Sieving of dispensed RM through mess 20, 40, 60

 Drying of Auxillary substances like starch, lactose, talc, Mg stearate, light MgO at 55º-60º C in
FBD/ Tray dryer for specified time
 Geometrical mixing of Active and Excipients in Cone blender for specified time (30-45 mins)
 Sampling of mixture for QC analysis
 Capsule filling process is then carried out by Semi-automatic Capsule Filling Machine after
release from QC.
 Sorting of capsule is carried out in Capsule Sorting Machine
 Polishing is done either in Capsule Polishing Machine or by rubbing in clean cotton towel with
little liquid Paraffin
 Finally capsule go for Primary Packing (Blister/Strip )
SR manufactures diff types of capsules as per the respective BMR. Here capsule are manufactured in ‘0’,
‘1’and ‘2’ size

Size Fill wt.( mg ) Wt. of Empty Gelatin (mg)

0 500 95

1 400 75

2 250 65

Equipments Used

 Sieve of mesh 20, 40, 60

 Double Cone blender (50 kg)
 Semi-Automatic Capsule Filling Machine SA 9 (Pam Pharmaceutical and Allied Machinery
Company)
 Automatic capsule filling machine
 Capsule Sorting Machine (Pam FS 100)
 Capsule Polishing Machine (Pam DP 100)
 Manual Capsule filling machine
 Dehumidifier

15
Semi-Automatic Capsule Filling -SA9

This machine works on principle of ''Volumetric Capacity'' filling. Parameters which should be adjusted in
this machine to achieve desired fill wt. are

 Auger speed
 Auger mechanism- to press powder down into capsule
 Higher the Auger Speed – Higher the pressure – Higher the fill wt.
 Turntable Rotational Speed
 Lower the Turntable Rotational Speed – Larger time for which each hole is under the Auger-
Maximum total fill wt.

Motor pulley A B C

X 3.4 2.7 4.3

Y 13.6 10.8 17

Z 6.8 5.4 8.5

For e.g Adjustment of pulley Y to C = 17 → Higher turntable speed

Adjustment of pulley X to B = 2.7 → Lower turntable speed

Types of Auger
SR makes use of 4 types of Auger

1. Standard Auger or Single Flute Auger

 Used for most of the powder

2. Spiral Auger or Double Flute Auger

 Used when bulk density of powder is low

 Used when powder resist to flow down
 used when you get low wt. than desired wt. even at slowest speed of turntable
3. Four flute Auger

 Is used for powder having high bulk density

16
  Is used when you get higher wt. with standard auger even at highest RPM of turntable
4. 90ºAuger

 Is used when you get higher wt. with standard auger and lower wt. with four flute auger
Temp and humidity is controlled in capsule section by dehumidifier. At high moisture levels, capsule
absorbs moisture and become soft, tacky. At low moisture level, capsule becomes very brittle. Both of these
changes cause handling problem in filling equipment.

Temp and RH are maintained at

Temp = 25 ± 2 ºC RH = 45 ± 5 %

Flow chart for overall process of Capsule Production

RM

QC analysis RM requisition from production

↓ ↓

QC release → RM dispensing ← supervised by QA

by store

Sieving

Drying of auxiliary substances

Mixing in cone blender

QC release

Capsule filling

17
 Sorting

Polishing

QC release

Packing

DRY SYRUP SECTION

SR produces many Penicillin products in Dry Syrup form. Dry Syrup section is segregated through Airlock.
During prepn and filling of dry syrup, environment should be dry. Presence of appreciable amount of
moisture will deteriorate the product and flakes will be seen before the product expires. Thus, prep n and
filling of dry syrup is carried out in Humidity and Temp controlled room through use of Dehumidifier.
Humidity and temp of this room is checked by IPC at frequent interval which should be:

Temp = 25 ± 2 ºC RH less than 39 %

Equipments used

 Automatic Single Head Powder Filler (Mars Mech APF-99)

 Sealing Machine (Konark machine tools)
 Dehumidifier 

Steps Of Dry Syrup Preparation

 Milling of sucrose in Multimill

 Sieving of RM
 Drying of sucrose in FBD
 Moisture test of sucrose in QC (NMT 2%)
 Geometrical mixing of active and excipients in Cone blender
 Sampling of mixture for QC analysis
 Cleaning of HDPE Bottle and Inner cap with compressed air

18
  If approved by QC, filling of dry syrup in HDPE bottle in Automatic Single Head Powder Filler (
Mars Mech APF-99 )
 Plastic Inner seal is placed manually and outer ROPP cap sealing is done in Sealing Machine (
Konark Machine Tool )
 IPC wt. variation test and leak test
 Labeling and packing

SR Has Been Preparing Dry Syrup Of Following Wt.

Fill wt. ( gm ) Volume make up ( ml ) ± % variation

45 90 2

30 60 2

22.5 45 2

15 30 2

5 10 4

Liquid section
In liquid section, different suspensions, syrup and drops are manufactured. The water used for the
preparation is De-Mineralized Water. Products are then filled in different sized bottles as 10, 15, 30, 60,
100, 150, 200 ml.

Equipments Used

Fig.8 Mixing tank with Heating jacket and Fig.9 Colloid mill
stirrer

19
Primary Syrup Preparation Room

 Manufacturing / Mixing tank with Heating jacket and stirrer

Liquid Manufacturing Room

 Manufacturing / mixing tank with heating jacket

 Homogenizer
 Filter press (Havell’s India Ltd)
 Heating vessel
 Colloid mill ( Chamunda )
 Transfer pump ( Bgartia Cutler Hammer)
 SS liquid Transfer pipe
Liquid Hold

 Storage tank
Bottle Washing

 Rotary Bottle Wash

 Turntable (Konark Machine Tool)
Liquid Filling and Sealing

 Liquid filling and sealing machine (Monoblock 6|6)

Process
 First the base is prepared which may be sucrose (70-80% w/v) or 70% sorbitol. The temp of sucrose
syrup should be maintained below 90º C because above 90º, caromelization of sucrose occurs.
 Then the active and other constituents are added and homogenized continuously.
 Final volume is made up with DM water.
 pH is checked at room temperature, prior to which pH meter is calibrated with standard electrode
buffer of pH 7 and pH 4.
 pH is adjusted with sodium citrate or citric acid.
 Filtration of syrup is carried out in filter press which consists of 9 filter pads (Nylon) of mess 200.
Hyflow supercel powder is used as filter aid.
 Suspension is passed through colloid mill for homogenization and particle size reduction. Then it is
passed through desirable mesh. E.g., for Nocid = 80 mesh, for Zenosar = 40 mesh, Vitacal = 200
mesh etc.
 Empty bottles are washed with RW and DM water

20
 Empty bottles are checked for spots and cracks
 Filled bottles after sealing are checked for improper sealing, particles and insufficient volume

Flow chart for overall Process of Liquid Production

RM

QC analysis RM requisition from production

↓ ↓

QC release → RM dispensing ← supervised by QA

by store

Sieving

Primary syrup/base preparation

Mixing of active and other excipients

Volume make up

Homogenization

PH adjustment

QC release

↙ ↘

Filtration in filter press colloid mill for suspension

for syrup ↓

21
 passed through mesh 60 or 40
↘ ↙

Storage tank

Bottle washing

↓
Empty bottle inspection
↓
Bottle filling and sealing → IPQA volume check
↓

Filled bottle visual inspection

Labelling and packaging

Ointment Section:
In SR, ointments are manufactured by fusion method. The process involves:

 Melting of solid ingredients, bases in decreasing order of their melting points

 Adding active ingredient to the melted ingredients
 Stirring thoroughly until a homogenous product is formed

Fig.10 Ointment manufacturing plant Fig.11 Filling machine

22
Equipments Used

 Wax vessel
 Manufacturing vessel
 Storage vessel
 Filling, Crimping and Batch coding machine
 Electronic balance
Ointment Manufacturing Process:
Raw and packing material store

↓
Dispensing day
↓
store
↓
Shifting/milling
↓
Preparation of aqueous phase in planetary mixture (with continuous stirring)
↓
Preparation of oil phase in vessel with stirrer (with continuous stirring)
↓
Transferring of oil phase into aqueous phase by vacuum transferring system
↓
Mixing with continuous stirring
↓
Transfer of content to the storage tank
↓
QC release
↓
Tube filling finished
↓
Product quarantine QC
↓
Release
↓
Finished goods area
↓
23
 QA release
↓
Release for sale

ORS Section

SR manufactures ORS which is a type of fluid replacement used to prevent dehydration. It consists of a
mixture of dextrose, sodium chloride, potassium chloride and sodium citrate.
Equipments Used
ORS filling machine(uflex)

ORS Manufacturing Process

RM requisition by production
↓
RM dispensing
↓
Salts are dried in FBD for 2 hours
↓
Active constituents are geometrically mixed with excipients
↓
Sieving in shifter

Milling in multimill

Blending in blender

Filling and packing in ORS filling machine

External Preparation Section

Various kinds of external preparations such as lotions, pastes, sanitizers are prepared in this section.
24
 Fig.12 Manufacturing Tank Fig.13 Automatic Liquid Bottle Filling Machine

Equipments Used For Sanitizers

 Mfg(manufacturing) tank
 Holding tank
 Filling tank

Equipments Used For Pastes And Lotions

 Paste making machine(precikot)

Packaging
Packaging provides presentation, protection, identification, information, containment, convenience and
compliance for a product during storage, carriage, display and use. Packaging may be:

Primary Packaging

Secondary Packaging

Primary Packaging
In primary packaging, product is in direct contact with the packaging material. The room for primary
packaging is maintained at optimum temperature and relative humidity. Primary packaging is done in
grey area whereas secondary packaging in black area. Various instruments available in the packaging
room are:

 Strip packing machine

 Alu-Alu packing machine
 Blister packing machine
25
  Hygrometer
 Dehumidifier

Strip Packaging

For the products that are highly sensitive to light and moisture strip packaging is done. The primary
packaging material is opaque plastic-coated aluminum foil, which provides barrier, to light and moisture.
This packaging is expensive compared to blister packaging. Packaging is carried out by automatic
machine consisting of two heaters, one for heating Aluminum foil and the next for sealing. Thepackaging
material is previously printed with the information about the product and the batch number, manufacturing
date, expiry date are printed simultaneously in the machine itself during the packaging. The pocket formed
varies depending upon the size of tablets and capsule. After sealing, they are cut into desired strip and are
directed towards the secondary packaging room.

Parts Of A Strip Packaging Machine:

 Hopper: for feeding

 Plate: for guiding the tablets from the hopper into the chute
 Printing assembly: to print the batch no. , mfg. date, exp. Date, price on the plain Al foil
 Chute: for passing the desired no. of tablets into the foils between the rollers
 Heater: heat the foil
 Roller: for sealing the dose contained within the two heated foils
 Cutter: for cutting the required size strips.

Fig.14 Strip Packaging Machine

26
 Flow Chart Of Strip Packaging:
Laminated Aluminum foil is imprinted with the Batch no. exp. Date, mfg. date etc.
Aluminum foil is heated
↓

Tablets are fed in hopper which gets vibrated via vibrator and comes in motion

Pockets are formed due to the pressures exerted by tablets/capsules

Tablets gets into track via chute and gets filled into the aluminum foil

Sealed by the overprinted aluminum foil

Cut into desired strip size by automatic cutter

Drugs from the primary packaging passes through the conveyer’s belt for secondary
packaging (black area)

Blister Packaging
It is used for the products that are not sensitive to light and moisture. The film heater heats the polyvinyl
chloride and polyvinyl dichloride and creating vacuum and heating forms the pockets. These pockets are
released after cooling. When the tablets and capsule is filled in each pocket, printed aluminum foilis
rolled over the filled pockets and then sealed by heating. After sealing they are cut into desired blister
size and directed towards secondary packaging.

Parts Of A Blister Packaging Machine

 Hopper, feeder, feed track, guide track, vibrator

 PVC holder, forming roller, sealing roller,
 Strip cutter, cutting gear, forming heater, sealing heater
 Control panel

27
 Flow Chart Of Blister Packaging:
Aluminum foil is imprinted with the batch no, exp date,mfg date etc

PVC is heated
↓

Tablets are fed in hopper which gets vibrated via vibrator and comes in motion

Pockets are formed in PVC foil via vacuum pressure exerted in blister roller tablets/capsule

gets into track via hopper and gets filled into the blister formed in the PVC

Sealed by the overprinted aluminum foil

Cut into desired strip size by automatic cutter

Drugs from primary packing passes through a conveyer belt for secondary packaging (black area)

Alu-Alu Packaging:
This is similar to blister packaging in many aspects. Lidding foil is same as blister

packaging but base foil is made up of aluminum. Base foil is used in forming blister with the application
of mechanical pressure. High protection to light and moisture and attractive appearance are the advances
of the Alu-Alu packaging as compared to the other. The process of forming of the pockets and the
packaging process is same as that of the blister packs.

Secondary Packaging

Secondary packaging refers to further packaging of primary packed materials in duplex box and then it
undergoes shrink packing. Finally, it is packed in large corrugated box and stored in finished product
quarantine room then transferred to finished product approval from QC. As this section falls in black area
separate entry is made with the change room.

28
Equipments Used In Secondary Packaging

o Auto High-Speed Labeling Machine 150 M/C (Konark)

 For labeling of Bottles
o Film Wrap Shrink Machine
 For film wrapping of bottles
Shrinking temp = 250 ºC Shrinking time = 1 sec

o Leak Test Apparatus (Scientech)

 4-5 strips of blister/strip pack are immersed in water for 1 min under vacuum:
Strip = 600 mm Hg

Blister = 500 mm Hg

Dry Syrup = 300 mm Hg

 After 1 min, strips/blisters and seals are unfolded to check if there is water permeation
 Leak test is usually carried out
After first setting
After foil change
Doubt – problem in foil
For bottles (liquid preparation), leak test is carried out by placing the bottle in inverted position for 1 hr.

After final packing, products are kept in FG quarantine Hall until QC Release Slip is obtained.

Activities Done In Secondary Packaging Room:

 Visual Inspection : tablet c a p p i n g , breaking, empty blister or strip as well as

overprinting and logo are checked
 Weighing
 Cartons are overprinted with batch number, manufacturing date, expiry date and
maximum retail price.
 Strips and blisters are packed in the overprinted carton (Duplex Box).
 These cartons are packed in fiber board containers/Corrugated case and labelling is done.

Overprinting Section
Additional matter or another color printed onto a previously printed sheet is known as
overprinting. In overprinting section following things are inspected:-

 Side cutting
 Overlapping printing
 No leaflets in Duplex box
 Alternate batch no in packaging box

29
  Color change of labels
 Misprinting in packaging box

Production Change Over

Change-over is done for the manufacturing of new product or new batch product. It includes the cleaning
of manufacturing section and all the associated equipment. The cleaning process includes the following:

 Washing of room and equipment with water and liquid soap

 Drying the room
 Cleaning by isopropyl alcohol or kerosene

After the cleaning process is over, swab test is done. If the test is passed then request for line clearance
for new product is made. First approval is made by production officer and request is send to QA for
approval. As QA officer approves, line clearance is granted and new product manufacturing is started.

Store

Storage is the process of keeping or holding goods in a systematic way preserving its quality and store is
the place where goods are kept safely for future use. Store is the first point of entry of material into the
factory and the last point at which the factory still has control of its product before they leave to go to a
customer. Store should therefore be properly maintained to prevent deterioration, contamination of stored
goods.

Store of SR is very spacious and properly designed to ensure good storage condition. Store of SR is divided
into different section

1. RM store 2. PM store 3. FG store

These sections are further separated into Quarantine, Approved, Narcotic and Thermal control section.

There is provision of different store for Penicillin, Cephalosporine and Non-Pen products. RM and PM of
Non-Pen products are stored in ground floor. RM and PM of Pen products & Cepha Products are stored in
2nd floor. Penicillin is in separate building.

RM and PM Store

Store receives different RM and PM from different vendors. (60% from India)

 RM and PM are first received in receiving room with a copy of an invoice.

 Store in-charge inspects the intactness of the seal on container and checks if quantity received is as
specified in an invoice or not.

30
  Containers are de-dusted and all the required information like Batch details, Exp date, Name of
supplier etc. is noted.
 Store in-charge assigns the control number and enters the received material in Store Receiving
Report (SRR), warehouse daily report, RM ledger and PM ledger.
 Based on SRR, official label is prepared and attached to respective container which is taken to
Quarantine Area.
 Color discrimination is used to separate Quarantine and Approved area.
 Cabinets inside yellow borderline indicate quarantine section and that inside green borderline is for
approved section.
 Store sends SRR & RM test request note to QA for sampling and analysis.

 QA carries out sampling of RM in sampling booth and tags 'Undertest- Yellow' label on sampled
container.
 The materials are kept in quarantine till QC claims the material to be approved for further use. After
being approved the material is tagged with 'Green Approved' label.
 Location no. is given to approved RM and PM which are kept orderly in approved area.
 Rejected samples are tagged with 'Red rejected label' and quickly removed from quarantine to
rejection store to avoid mix-up.
 Dispensing of RM/PM for a batch is done in the dispensing booth in presence of officer from store
and QC on receiving RM/PM requisition Slip from production which in turn is issued on release of
BMR or BPR from QA.
 Amount of RM and PM received and dispensed each time is entered in RM and PM register book
showing balance/amount remained.
 Narcotic RM like Codeine phosphate and Alprazolam are kept separately in a cabinet with locker.
 Thermolabile materials like Hard Gelatin capsule, vitamins, gentamycin etc. are stored in a separate
AC room.
Secondary PM Store

Secondary PM like cartons, FBC are stored in a different room located in top floor. While PM like bottles
are stored in a different room outside the main building.

Finished Product Store

Finished products received from packaging unit are kept in FP Quarantine Hall. FP are not delivered to FP
release store until FP Delivery Note is released by QC. After getting release note from QC, FG transfer
advice is prepared by packing in-charge and sent to store in-charge. Store then moves FG from quarantine
to FG release store and assigns location no. FG are kept orderly and safely according to location no. which
31
helps in easy traceability. Delivery of finished product is done only upon request from sales department.
Delivery of FG also follows FEFO and FIFO system. FG store in-charge dispatch the FG goods as
mentioned in Challan received from Head Office and fax details about product and quantity being
dispatched to Head office. Gate pass is prepared for all quantities being dispatched which is verified by
security personnel at the gate. Dispatch FG goods are loaded in Delivery van and dispatched to the
destination place viz. Distributors, Super stockiest etc.

FG store also receives the returned and expired product from distributor which is segregated into different
area to avoid mix-up. In case of returned goods with long expiry, they are re-circulated to another party. In
case of expired products, withdrawal and destruction note is prepared by store which is approved by QC in-
charge, management and QA chief. Then in presence of QC, expired products are destroyed scientifically.

Master List Of Record In Store

o Daily balance calibration book

o Daily cleaning book
o Daily dispensing record book
o Letter (loan issued and received)
o Packing material sampling book
o PM invoice
o PM ledger
o PM location book
o PM SRR returned by QC
o RM receiving record book
o RM sampling book
o RM invoice
o RM location book
o RM ledger
o RM SRR returned by QC
o RM/PM rejection record book
o SRR issued log book to QC
o Stock adjustment memo
o Auxiliary invoice

32
 Quality Control Department

''Quality is never an accident ''.

To build quality in the end product, overall control should be maintained right from the starting material to the
manufacturing processes, building design, equipment and personnel involved. In order to deliver quality drug
to the people, SR has been implementing Good Manufacturing Practice which ensures that products are
consistently produced and controlled according to the quality standards.

In order to control the quality of product and assure that all the processes and practices meets GMP
requirements, SR has a monitoring body called Quality Control Department. QC performs analysis as per the
official Pharmacopoeias and other validated procedures like In-House Specification ( IHS) to check if the tested
materials meet the specification or not.

QC Activity
QC is that part of GMP which ensures that necessary and relevant tests are actually carried out and products
are not released until judged satisfactorily.

QC lab is equipped with sophisticated equipments, various chemicals, reagents and trained pharmacists and
analysts are involved in following major activities-

 Raw material analysis

 In process sample analysis
 Finished product analysis
 Packaging material analysis
 Maintaining quality control test records of all the analysis i.e. RM, PM, IPS.
 Maintaining proper RM and Finished product control sample and performing real time stability study.
 Calibration and standardization of laboratory equipments
 Sampling
 Dispensing
 Line clearance
 Bio-burden test
 Daily water analysis
 To implement GLP to reduce quality control loss
 To ensure that the appropriate validation are done
 To check the maintenance of each department, premises and equipment

33
  To ensure that the requ ired initial and continuing training of each department personnel is carried
out and adapted according to need.
 Approve or reject, starting materials, intermediate and bulk materials
 To ensure that all necessary testing is carried out in accordance with the correct approved
methods
 To approve specifications, sampling instructions, test methods & other quality control procedures
 To provide overall direction for the operations in chemical and microbiological laboratory, in process
control and GMP & GLP implementation

The various sections and equipments/instruments in this department are as follows:

Documentation Room

Document maintained by QC department:

 Testing and release of final product

 Testing and release of intermediate product
 Analytical assays
 Sample: test and retention
 Summary protocol of QC results
 Stabilities studies
 Reference standard and control (maintenance and testing)
 Re-certification/Re-calibration of QC equipments
 Preparation of reagent & material for QC test

Instrumentation Room
 UV- Vis Spectrophotometer (Shimadzu1700)
 Polarimeter (Scope enterprises)
 Photofluorometer 152 (Systronics)
 Vortex mixer (Sonar)
 Electronic balance (Shimadzu)
 Melting point apparatus (Campbell)
 Karl fischer apparatus (Systronics)
 HPLC (Shimadzu)
 Refractometer (Atago)

34
Chemical Analysis Lab
 Various chemicals and reagents
 Magnetic stirrer with hot plate- 4
 Distillation plant
 Flame photometer (Systronics)
 Fuming cupboard
 Conductivity meter (Deluxe R 216)
 Dissolution test apparatus (Electrolab TD-TO8 L)
 Tablet Disintegration test machine (Campbell electronics)
 Centrifuge apparatus (Campbell electronics)
 Power density tester (Campbell electronics)
 Friability tester (Campbell electronics)
 Tablet hardness tester (Campbell electronics)
 PH meter (Systronics)

Heating Room
 Ultrasonic bath (sonicator)
 UV cabinet (Ultra-vision)
 Muffle furnace (Thermotech)
 Vaccum oven (Osworld)
 Autoclave (Osworld)

Stability Room
 Hot air oven -A (Osworld)
 Hot air oven –B (Osworld)
 Humidity chamber (Osworld)

Microbiological Section
 Laminar Air Flow Bench (Airpac)
 Incubators –2(Hicon, Osworld)
 Zone reader (Campbell)
35
  Colony counter (Osworld)
 Refrigerator (Samsung)
 Autoclave (Life)
 Micrometer (Mitutoyo)
 Vernier callipers (Mitutoyo)
 Microscope
 Micropipette (Brand)

Sampling Intimation/Release/Rejection Of Raw Materials/Packaging Materials

Receipt and inspection from warehouse

AR no entry and allocation issue of protocol and specification

Identification test

Identify and test comply

Complete analysis on pooled sample

↙ ↓ ↘

Material passing intimation to materials rejected in the test

all tests store follows OOS procedure as per

SOP

↓ ↓ ↓

Affix the approved label ↓ verification of analysis

on each container material against the control sample

transfer to predetermined

location

36
 ↓

↙ ↘
QC approval raw intimation to
materials are available purchase
for use in production

Quality Assurance Department

Quality Assurance is a wide-ranging concept covering all matters that individually or collectively influence
the quality of the products. It is the totality of the arrangements made with the object of ensuring that
pharmaceutical products are of the quality required for their intended use. Quality assurance therefore
incorporates GMP along with products design and development.

Quality assurance encompasses a scheme of management which embraces all the procedures necessary to
provide a high probability that a medicine will conforms consistently to a specific description of a quality.

ISO defines QA as “the assembly of all planned and systematic actions necessary to provide adequate
confidence that a product, process, or service will satisfy given quality requirement.’’

It covers all matters that may individually or collectively influence the quality of a product. It overlooks Total
Quality Management System. S.R. Drug Laboratories Pvt. Ltd have well organized systems and documents.
The department is concerned with establishing control.

Functions of QA department

 Documentation (BMR, SOPs, Site master file, master formula record etc
 Validation
 Vendor selection and development

37
  Cleaning and sanitization
 Environmental monitoring program
 Label control program
 GMP and ISO training
 Qualification of equipment
 Complaints handling and product recalls
 Internal audit and self-inspection
 Release/reject of product and materials
 Line Clearance
 Assuring Quality of products:
 SOP compliance
 Record Verification
 Release of Batch Manufacturing
 Stability of product

QA department usually handles:

 Checking and approval of documents generated based on BMR

 Assure the validation of manufacturing procedure
 Assure regulating & company standard
 Documentation control
 Controlled distribution and archiving of documents
 control of changes made by proper approval of all documents

Documents Maintained By QA Department

 Site Master Plan

 Quality manual
 Batch Record Review
 Product Specification
 Inspection/Internal Audits
 Validation Protocol Approvals
 Product Recall
 Product Complaints

38
  Contractor Audit
 Vendor Audit
 Document control, Revision and Distribution
 Employee Records, Health Records
 Training (Technical and GMP)
 Preparation of SOPs, BMRs, BPRs
 Adverse event reports
 Change control
 Engineering records
 Pest control records
 Storage Temperature Monitoring
 Product Distribution Procedure
 Distribution Records
 Quarantine, Release, Rejection and Storage
 Master Validation plan
 Sampling log book
 Record book of active materials

MAINTAINANCE

AHU (Air Handling Unit)

There are different air-handling units that maintain the unidirectional airflow separately for different rooms in
production departments, corridor, packaging section. Each room is provided with supply filter (5 µ) for inlet
of air at the top of the room and return filter (10 µ) for outlet of air at the opposite side on the bottom of the
room. Pressure cascade corridor must be positive to operating room with 15 Pascal’s difference which is
maintained through controller.

There are altogether 10 AHU unit in SR

39
AHU 1: For Tray dryer, Washing, Granulation and Dispensing

AHU 2: For Compression, Blending, Quarantine, Tablet Inspection and IPQC

AHU 3; For Blister Packing, Strip Packing, ORS Filling and Capsule Filling

AHU 4: For Coating and Primary Syrup

AHU 5: For Liquid Section

AHU 6: For Corridor

AHU 7: For Secondary Packaging

AHU 8: For Penicillin Production

AHU 9: For Penicillin Corridor

AHU 10: For Ointment

Fresh Air Recirculated Air

Inlet Duct Prefilter/ Fibrous Filter (5µ) Bag Filter (20µ)

Outlet Duct Heater (Solonoid Coil) Condensing Unit (Chiller)

Controller Supply Filter/ Room Return Filter

Biopack Filter

Fig.15 Air Handling Unit

40
 Effluent treatment plant [ETP]
This is the biological process in which the effluents are biologically treated with the aid of bacteria grown
in the effluent plant. In this plant, basically air is diffused in to the water with the help of aeration pump
continuously. Aerobic bacteria which are grown in the aeration tank before and will act on the organic
load prevent in effluent.

More over passing through the sand filter and carbon filter provided in the plant, purified water with
maintained BOD, COD is discarded to environment. This ETP helps in the industry to be environment
friendly by helping reducing environment pollution.

RO Water Production
The primary goal of this system is to generate pharmaceutical-grade water. The water supply system is carefully
designed to create a closed-loop arrangement, ensuring a constant circulation of water and preventing
stagnation around the taps, where small amounts of water can accumulate. The water purification system plays
a crucial role as it directly impacts the quality of the final product. To produce pharmaceutical-grade water, a
reverse osmosis (RO) process is employed. The system features a dual-pass reverse osmosis water system
provided by SR, which continuously generates purified water and distributes it to all departments

41
BRANDS OF MARKET FORMULATION BY COMPANY:

BRAND NAME GENERIC NAME USE

ACEPRIL 2.5 Enalapril maleate 2.5 Treat high blood pressure and
heart failure

ACIDIN 150 RANITIDINE HCL 150mg To treat ulcers

ACIV ACYCLIVIR 5% W/W Anti- Virus

ALASTIN 10 Ebastine 10 mg ANTI- ALLERGIC

AM-CLAV AMOXYCILLIN & POTASSIUM ANTIBIOTIC

CLAVULANATE

42
 CONCLUSION

We are delighted to express our gratitude to SR Drug Laboratories Pvt. Ltd., the leading pharmaceutical company
in Nepal, for providing us with an invaluable opportunity and platform to undergo our in-plant training. This
experience allowed us to immerse ourselves in the real working conditions of the pharmaceutical industry,
enabling us to study the organization and functioning of a pharmaceutical company firsthand.

Despite the relatively short duration of the training period, we were able to acquire practical knowledge and gain
insights that will prove beneficial throughout our academic and professional careers. The support and guidance
provided by both technical and non-technical personnel greatly aided our understanding and learning of
fundamental and practical aspects of pharmaceutical manufacturing, analysis, and regulatory processes.

This training served as a crucial steppingstone towards our professional careers, instilling within us a sense of
self-confidence and equipping us with the ability to effectively integrate theoretical knowledge with the practical
skills acquired during the training period.

43