Industrial Training Report

ON
TABLET, CAPSULE, PACKAGING & QUALITY CONTROL

AT

LUCKNOW

PREM KUMAR CHAURASIA

B.PHARM, FINAL YEAR

SHAMBHUNATH INSTITUTE OF PHARMACY,

ALLAHABAD

WWW.PHARMANOTES.ORG
TRAINING CERTIFICATE
 SHAMBHUNATH INSTITUTE OF PHARMACY
JHALWA, ALLAHABAD

CERTIFICATE

This is to certify that Mr. Prem Kumar Chaurasia, Student of SHAMBHUNATH INSTITUTE OF
PHARMACY, ALLAHABAD. Has been completed industrial training in UTTAR PRADESH DRUGS &
PHARMACEUTICALS CO. LIMITED (UPDPL), LUCKNOW. At during the period, 20June to 19 July,
2012& submitted report on Production/Quality Control.
This work is done originally by students under my Supervision.
The industrial training was enriched with the knowledge & working culture of the respective company.

Mr. C.S.SINGH Dr. M.K.MISHRA

(Supervisor) (Director)

Shambhunath Institute of Pharmacy Shambhunath Institute of Pharmacy

Jhalwa, Allahabad Jhalwa, Allahabad
 DECLARATION

I hereby declare that the industrial project work embodied in this entitled, carried out by me under the
supervision of Mr. H.C.OLI. (Manager) UPDPL LUCKNOW.

I am indebted to my institutional guide, Mr. C.S.SINGH, SIP. ALLAHABAD for their step by step
guidance throughout the preparation of Industrial training report.
 ACKNOWLEDGEMENT

I am very thankful to production manager of U.P.D.P.L, Lucknow Pharmaceutical Company for giving me
permission for the training.
I want to give a lot of thanks to production manager Mr. H. C. Oli. Quality control manager Smt. Saroj Jain,
who supervised me for my future.
I have clean information about every instrument, manufacturing procedure and analytical methods.
A special thanks to all staff and workers who cooperate me during the training period.
Thanking you

PREM KUMAR CHAURASIA

B. Pharm. (Final Year)
Roll no- 0924150036
Shambhunath Institute of Pharmacy,
Allahabad.
 PREFACE

This report is prepared at Uttar Pradesh Drugs & Pharmaceutical Ltd, Lucknow.
The Uttar Pradesh Drugs & Pharmaceutical Ltd, Lucknow, is a Joint Enterprise of Central & Uttar Pradesh
government; producing pharmaceutical dosage products and distributing it in Uttar Pradesh government
hospital.

This report aims at identifying important inbound and outbound process for product formulation and its
problems.

The report is based on knowledge of topic relevant for the projects and discussions with the inbound &
outbound department in charges, and survey of the company.

The project is divided into five sections to simplify and distinguish the topics from each others.

During the project, I have concluded some analysis which is mentioned after each sub topics.
LAYOUT OF UPDPL
 COMPANY PROFILE

Uttar Pradesh Drugs and Pharmaceuticals Limited Lucknow.

This is a joint sector undertaking promoted by Indian Drugs and Pharmaceuticals Ltd (IDPL) and the
Pradeshiya Industrial Investment Corporation of Uttar Pradesh (PICUP). IDPL holds 51% of the equity
shares and the rest is with PICUP. The company was incorporated in 1978 and the commercial production
was established in October 1979. The company has its manufacturing unit and the registered office located
at Lucknow (Uttar Pradesh). The main products and pharmaceutical formulations are in the form of Tablets,
Capsules, Powders, Liquid Orals and Injectables.

The Board for Industrial and Financial Reconstruction (BIFR) formally declared the company as sick on the
30th December, 1992. After prolonged and sustained efforts, a revival package for the company was
sanctioned by the BIFR on the 22nd August, 1995. The revival period was for ten years beginning from
1995-96. However, before the revival package could be put into operation, the two bankers, namely, the
Bank of Baroda and the Indian Bank and one of the promoters, namely PICUP, went in appeal against the
sanctioned scheme to the Appellate Authority of Industrial & Financial Reconstruction (AAIFR). The
Appellate Authority through its order dated 14.10.1996 set aside the sanctioned scheme and remanded the
case back to the BIFR.

The case of UPDPL is still before the BIFR. In the hearing held on 27.8.1997, the BIFR passed directions
that one time settlement of the dues of banks should be negotiated by PICUP, one of the two promoters of
UPDPL. The Operating Agency was directed to update and prepare a revised package and the promoters
directed to make all efforts to bring in the requisite equity support. As there was no progress, in the hearing
held on 4.2.1999 BIFR directed the MD, UPDPL to submit a comprehensive rehabilitation proposal. This
has since been submitted by the company. Matter has been reviewed by BIFR again on 20.12.99 and they
have passed.

Directions that Operating Agency may explore possibility for change of management through any private or
public body, as also sale of the company without liabilities. Concurrently the GOI has been asked to finalize
their stand on possibility of supporting the UPDPL through a fully tied up rehabilitation proposal.
 CONTENTS
Page no
1. Tablet section 1-30

Topic Page No.

Tablet 1

Ingredients used in tablet formulations 3

Granulation 9

Blending 13

Sieving 14

Dryer 16

Tablet punching 16

Tablet coating & type of coating 19

Some common problem in tabletting 28

U.P.D.P.L. Product list (Tablet) 30

2. Capsule section 31-40

Topic Page No.

Capsule 31

Type of capsule 32

Additives 34

Manufacture of heard gelatin capsule 35

Filling of heard gelatin capsule 36

Finishing 38

U.P.D.P.L. product list (capsule & powder) 40

3. Quality control 42-61

Topic Page No.

Quality Assurance & Quality Control in Pharma Industry 41

Quality Control work (Summary 42

Quality control department 42

Chemical section 45

Instrumental section 49

Micro-biological section 56

4. Packing section 62-66

Topic Page No.

Packaging & it’s type 62

The purposes of packaging and package labels 64

 LIST OF ABBRIVATION
CGMP = Current Good Manufacturing Process

D.M. Water = Demineralized Water.

EC = Ethyl cellulose

GIT = Gastrointestinal tract.

GMP = Good Manufacturing Process

HPMC = Hydroxy Propyl Methyl Cellulose.

HPC = Hydroxy Propyl cellulose

MHEC = Methyl Hydroxy Ethyl Cellulose.

PEG =Polyethylene Glycol.

SCMC = Sodium corboxy methyl cellulose.

 TABLET SECTION
Tablet
A tablet is a mixture of active substances and excipients, usually in powder form, pressed or compacted into
a solid. The excipients include binders, Glidants (flow aids) and lubricants to ensure efficient tabletting,
disintegrates to ensure that the tablet breaks up in the digestive tract; sweeteners or flavors to mask the taste
of bad-tasting active ingredients; and pigments to make uncoated tablets visually attractive. A coating may
be applied to hide the taste of the tablet's components, to make the tablet smoother and easier to swallow,
and to make it more resistant to the environment, extending its shelf life.

Advantage
• Production aspect
Large scale production at lowest cost
Easiest and cheapest to package and ship
High stability

• User aspect (doctor, pharmacist, patient)

Easy to handling.
Lightest and most compact.
Greatest dose precision & least content variability.
Coating can mark unpleasant tastes & improve pt. acceptability.

Disadvantages
• Some drugs resist compression into dense compacts.

• Drugs with poor wetting, slow dissolution, intermediate to large dosages may be difficult or
impossible to formulate and manufacture as a tablet that provide adequate or full drug
bioavailability.

• Bitter taste drugs, drugs with an objectionable odor, or sensitive to oxygen or moisture may require
encapsulation or entrapment prior to compression or the tablets may require coating.

Types of tablets
1. Route of administration
a) Oral tablets,
b) Sublingual or buccal tablets,
c) Vaginal tablets,

2. Production process
a) Compressed tablets,
b) Multiple compressed tablets,
Tablet within a tablets: core and shell,
Multilayer tablet Sugar coated tablets,
 Protect tablets from moisture,
Mask odor and flavor,
Elegance,
Film coated tablets,
Thin film coat,
Soluble or insoluble polymer film,
c) Chewable tablets
Rapid disintegrate,
Antacid, rapid action,
Children drug,
d) Effervescent tablets
Dissolve in the water before drink,

Ingredients used in tablet formulations

1. Drugs.
2. Fillers, diluents, bulking agent
To make a reasonably sized tablet.
3. Binders
To bind powders together in the wet granulation process.
To bind granule together during compression.
4. Disintegrates
To promote breakup of the tablets.
 To promote rapid release of the drug.
5. Lubricants
To reduce the friction during tablet ejection between the walls of the tablet and the walls of
the die cavity.

6. Glidants
Reducing friction between the particles.
To improve the flow properties of the granulations.
7. Antiadherants
To prevent adherence of the granules to the punch faces and dies.

8. Dissolution (enhancers and retardants)

9. Wetting agents
10. Antioxidants
11. Preservatives
12. Coloring agents
13. Flavoring agents
Direct compression fillers
• Common materials that have been modified in the chemical manufacturing process to improve
fluidity and compressibility.

1. Soluble fillers
a. Lactose
i. Spray dried lactose
• Lactose is placed in aqueous solution, removed impurities and sprays dried.

• Mixture of large alpha monohydrate crystals and spherical aggregates of smaller crystals.

• Good flowability but less compressibility.

• Poor dilution potential.

• Loss compressibility upon initial compaction.

• Problem of browning due to contamination of 5-hydroxyfurfural which was accelerated in the

presence of basic amine drugs and catalyzed by tartrate, citrate and acetate ions.

ii. Fast-Flo lactose (early 1970s)

• Spherical aggregates of microcrystal’s lactose monohydrate.

• Held together by a higher concentration of glass (amorphous lactose).

• Much more compressible.

• Highly fluid.

• Non hygroscopic.

• Tablets are three to four times harder than regular spray dried.
 iii. Tabletose: aggromerate form of lactose
• More compressible than spray dried but less compressible than Fast Flo lactose.

iv. Anhydrous lactose: free flowing crystalline lactose

• Produced by crystallization above 93C which produces the beta form.

• Pass through steam heated rollers.

• Good flow property, contained high amount of fines, its fluidity is less than optimal.

• Can be reworked.

• At high RH anhydrous lactose will pick up moisture forming the hydrated compound increase
in the size of tablets if the excipients make up a large portion of the total tablet weight.

• Excellent dissolution property.

b. Sucrose
i. Di-Pac: co crystallization of 97% sucrose and 3% modified dextrin
• Small sucrose crystals glued together by dextrin.

• Good flow properties and needs a Glidants only when atmospheric moisture levels are high
(>50%RH).

• Excellent color stability on aging.

• Concentration of moisture is extremely critical in terms of product compressibility.

• Compressibility increases rapidly in a moisture range of 0.3-0.4%, plateaus at a level of 0.4-

0.5% and rises again rapidly up to 0.8% when the product begins to cake and lose fluidity.

• Dilution potential 20-35%.

• Tablets tend to harden slightly during the first hours after compression or when aged at high
humidity’s and then dried (this is typical of most direct compression sucrose’s or dextrose’s).

ii. Nutab: 95.8% sucrose, 4% convert sugar

• Equimolecular mixture of laevulose and dextrose and 0.1 to 0.2% each of cornstarch and
magnesium striate.
• Large particle size distribution and good fluidity.

• Poor color stability.

c. Dextrose
i. Emdex: spray crystallized
• 90-92% dextrose, 3-5% maltose and the remainder higher glucose polysaccharides.

• Available both anhydrous and a hydrate product.

• Excellent compressibility.

• Largest particle size, blending problem may occur.

d. Sorbitol
• Exists in a number of polymorphic crystalline forms and amorphous form.
• Widely used in sugar-free mints and as a vehicle in chewable tablets.
• Cool taste and good mouth feel.
• Forms a hard compact.
• Hygroscopic and will clump in the feed frame and stick to the surfaces of the die table when
tableted at humidity’s > 50%.
• Lubricant requirements increase when the MC of the Sorbitol drops below 0.5% or exceeds 2%.
e. Mannitol
• Exists in a number of polymorphic forms.
• Not make as hard a tablet as Sorbitol.
• Less sensitive to humidity.
• Widely used where rapid and complete solubility is required.
• Use as a filler in chewable tablets.
• Cool mouth feels but expensive.
f. Maltodextrin
i. Maltrin
• Highly compressible.

• Completely soluble.

• Very low hygroscopic.

2. Insoluble fillers
a. Starch
i. Starch 1500: intact starch grains and ruptured starch grains that have been partially
hydrolyzed and subsequently aggromerate.
• Extremely high MC (12-13%).

• Does not form hard compacts.

• Dilution potential is minimal.

• Not generally used as filler-binder but as filler disintegrates.

• Retains the disintegrates properties of starch without increasing the fluidity and compressibility
of the total formulation.

• Deforms elastically when a compression force is applied, it imparts little strength to compacts.

• Lubricants tend to dramatically soften tablets containing high concentrations of Starch 1500.

• Spray dried starch.

ii. Era-Tab: spray-dried rice starch

• Good fluidity.

• MC 10-13%.

• Compressibility depends on moisture.

• Rework ability.
 • Low bulk density.

b. Cellulose
• Microcrystalline cellulose (Avicel)
• The most important tablet excipients developed in modern times.

• Derived from a special grade of purified alpha wood cellulose by severe acid hydrolysis to
remove the amorphous cellulose portions, yielding particles consisting of bundles of needlelike
microcrystals.

• PH102 more agglomerated, larger particle size, slightly better fluidity but not significant decrease
in compressibility.

• Most compressible.

• Highest dilution potential.

• A strong compact is formed due to the extremely large number of clean surfaces brought in
contact during the plastic deformation and the strength of the hydrogen bonds formed.

• Extremely low coefficient of friction, no lubricant requirement.

• When more than 20% of drugs or other excipients are added, lubrication is necessary.

• Not used as the only filler because of its cost and density.

• Usually used in the conc. of 10-25% as a filler-binder-disintegrates, rapid passage of water into
the compact and the instantaneous rupture of hydrogen bonds.

• Fluidity is poor because of its relatively small particle size, small amount of Glidants are
recommended in the formulations containing high conc. of MCC.

• Tablets are softening on exposure to high humidity’s.

• This softening is reversible when tablets are removed from the humid environment.

• More than 80% MCC may slow the dissolution rates of AI having low water solubility.

• Small particles get physically trapped between the deformed MCC particles, which delays
wetting and dissolution.

• This phenomenon can be overcome by adding portions of water soluble excipients.

c. Inorganic calcium salts

iii. Dicalcium phosphate (Emcompress or DiTab)
• Free flowing aggregates of small microcrystal’s that shatter upon compaction.

• Inexpensive and possesses a high degree of physical and chemical stability.

• No hygroscopic at a RH of up to 80%.

• Good fluidity.

• Slightly alkaline with a pH of 7.0 to 7.3.

• Precludes its use with AI that is sensitive to even minimal amounts of alkalinity.
 iv. Tricalcium phosphate (TriTab)
• Less compressible and less soluble, higher ratio of calcium ions.
Essential properties of tablet
• Accurate dosage of medicament, uniform in weight, appearance and diameter.

• Have the strength to withstand the rigors of mechanical shocks encountered in its production,
packaging, shipping and dispensing.

• Release the medicinal agents in the body in a predictable and reproducible manner

• Elegant product, acceptable size and shape.

• Chemical and physical stabilities.

Tablet production
Powders intended for compression into tablets must possess two essential properties-

• Powder fluidity
The material can be transported through the hopper into the die.
To produce tablets of a consistent weight.
Powder flow can be improved mechanically by the use of vibrators, incorporate the Glidants.

• Powder compressibility
The property of forming a stable, intact compact mass when pressure is applied.

Tabletting methods( Granulation )

• Dry methods
a) Direct compression

b) Dry granulation
• Wet methods
a) Wet granulation
1. Direct compression:-
Drug

Filler

Disintegrates Blending

Lubricant

Glidants Compression

E.g.:- Nacl, Nabr, Kcl.

• Tablets are compressed directly from powder blends of the active ingredient and suitable excipients.
 • No pretreatment of the powder blends by wet or dry granulation procedures is necessary.

Advantages
a) Economy
Machine: fewer manufacturing steps and pieces of equipment.
Labor: reduce labor costs.
Less process validation.
Lower consumption of power.

b) Elimination of granulation process

Heat (wet granulation).
Moisture (wet granulation).
High pressure (dry granulation).
Processing without the need for moisture and heat which is inherent in most wet granulation procedures.
Avoidance of high compaction pressures involves in producing tablets by slugging or rolls compaction.
Elimination of variability’s in wet granulation processing:
c) Binders (temp, viscous, age)
Viscosity of the granulating solution (depend on its temp).
Rate of binder addition and kneading can affect the properties of the granules formed.
The granulating solution, the type and length of mixing and the method and rate of wet and dry
screening can change the density and particle size of the granules, which can have a major effect on
fill weight and compaction qualities .

d) Type and rate of drying

Can lead not only to critical changes in equilibrium MC but also to un-blending as soluble active
ingredients migrate to the surfaces of the drying granules.
More unit processes are incorporated in production; the chances of batch to batch variation are compounded.

e) Prime particle dissociation

Each primary drug particle is liberated from the tablet mass and is available for dissolution.
Disintegrate rapidly to the primary particle state.

f) Uniformity of particle size

g) Greater stability of tablet on aging
Color.
Dissolution rate.
Fewer chemical stability problems would be encountered as compared to those made by the wet granulation
process.

h) Concerns
Excipients available from only one supplier and often cost more than filler used in granulation.
Procedure conservation, Machine investments, Lack of material knowledge.
 Physical limitation of drug -No compressibility, No flowability.
Physical characteristics of materials (both drug and excipients).
Size and size distribution-Moisture, Shape and surface, Flowability, Density.
Lotto lot variability, dusting problem, Coloring.

2. Wet granulation:-

Wet granulation is a process of using a liquid binder or adhesive to the powder mixture. The amount of
liquid can be properly managed, and over wetting will cause the granules to be too hard and under wetting
will cause the granules to be too soft and friable. Aqueous solutions have the advantage of being safer to
deal with than solvents.

Drug

Blending

Filler Adhesive

Wetting

Water

Granulation

Drying

Lubricant

Glidants Sizing

Disintegrates

Blending

Compression
3. Dry granulation:-

This process is used when the product needed to be granulated may be sensitive to moisture and heat.
Dry granulation can be conducted on a press using slugging tooling or on a roller compactor commonly
referred to as a chilsonator. Dry granulation equipment offers a wide range of pressure and roll types to
attain proper densification. However, the process may require repeated compaction steps to attain the
proper granule end point.
Also called as “Pre-compression” or “Slugging” method.

Drug

Filler Blending

Lubricant

Pre-compression

Comminution

Glidants

Lubricant Sizing

Disintegrates

Blending

Compression

E.g.:- Aspirin, vitamin.

Importance of granulation

1. To impart good flow properties to the material,

2. To increase the apparent density of the powders,
3. To change the particle size distribution,
4. Uniform dispersion of active ingredient.
Instrument for granulation

Blending
Powders to be used for encapsulation or to be granulated must be well blended to ensure good drug
distribution.
Inadequate blending at this stage could result in discrete portion of the batch being either high or low in
potency.
Steps should also be taken to ensure that all the ingredients are free of lumps and agglomerates.
For these reasons, screening and/or milling of the ingredients usually makes the process more reliable and
reproducible.

Equipment used for blending

V-blender.
Double cone blender.
Ribbon blender.

Slant cone blender.

Double cone blender

Scale up considerations
Time of blending.
Blender loading.

Size of blender.

Sieving
Separation of a mixture of various-sized particles, either dry or suspended in a liquid, into two or more
portions, by passing through screens of specified mesh sizes.

Importance of sieving
The sieving process gives three fractions of granules:
Very coarse granules, which return back to the milling process.
Very fine fraction, which return back to the compaction.

Fraction with optimal dimensions for following manufacturing steps.

Equipment used for sieving

Industrial Sifter and Sieving Machine-

Specifications:

Model Capacity Power

Sifter-20 100-120 Kg./Hr 1.0 HP
Sifter-30 150-180 Kg./Hr 2.0 HP
Dryer
In the pharmaceutical sector the fallowing dryers are use:
1. Static Oven,
2. Rotary Drier,
3. Fluidized Bed Drier,
4. Vacuum Oven,
5. Microwave Drier,
6. Spray Drier,
7. Rotary Atomizer,
8. I.R Drier.

TABLET PUNCHING

A tablet press is a mechanical device that compresses powder into tablets of uniform size and weight. A
press can be used to manufacture tablets of a wide variety of materials, including pharmaceuticals, illicit
drugs, cleaning products, and cosmetics. To form a tablet, the granulated material must be metered into a
cavity formed by two punches and a die, and then the punches must be pressed together with great force to
fuse the material together.

Tabletting procedure
• Filling,

• Compression,

• Ejection,

Tablet compression machines

• Hopper for holding and feeding granulation to be compressed.

• Dies that define the size and shape of the tablet.

• Punches for compressing the granulation within the dies.

• Cam tracks for guiding the movement of the punches.

• Feeding mechanisms for moving granulation from the hopper into the dies.

Single punch machine

• The compression is applied by the upper punch.

• Stamping press.
Multi-station rotary presses The rotary press has more than one set of tooling:-

The dies and the corresponding pairs of punches are arranged around a circular rotating turret.
Each individual die with lower punch in its lowest position, passes under the powder bed which is
contained within a feed frame, which in turn is fed from a hopper.
The die is completely filled under gravity, flow sometimes being assisted by rotating fingers in the
feed frame.
The quantity of solid in the die is adjusted by weight controlling cam.
These punches then pass upper punch to descend and the lower punch to rise.
 Thus the powder is actively compressed from both top and bottom faces.
The top punch then withdraws and the lower punch ascends as it passes over and ejection cam.

The tablet pressing operation an old Cad mach rotary tablet press

Tablets coating:
The coating in tablets, which is additional step in the manufacturing process.

Objectives:
To makes the taste, odor, or color of the drug.
To provide physical and chemical protection for the drug.
To control the release of the drug from the tablet.
To protect the drug from the gastric environment of the stomach with an acid resistant enteric coating.
Type of coating
1. Film coating.
2. Sugar coating.
3. Press coating.
4. Functional coatings

a) Enteric coating
b) Controlled release coating

1. Sugar coating
Traditionally sugar coatings formed the bulk of coated tablets but today film coatings are the more
modern technology in tablet coating.
Description of tablets: Smooth, rounded and polished to a high gloss.
Process: Multistage process involving 6 separate operations.

1. Seal tablet
core

2. Sub coating

3. Smoothing

4. Colouring

5. Polishing

Multistage process
1. Sealing tablet core- application of a water impermeable polymer such as Shellac, cellulose acetate
phthalate and polyvinyl acetate phthalate, which protects the core from moisture, increasing its
shelf life.
2. Sub coating -by adding bulking agents such as calcium carbonate or talc in combination with
sucrose solution.
3. Smoothing process -remove rough layers formed in step 2 with the application of sucrose syrup.
4. Colouring - for aesthetic purposes often titanium based pigments are included.
 5. Polishing - effectively polished to give characteristic shine, commonly using beeswax, carnauba
wax.
6. Printing -indelible ink for characterisation.

Tablet appearance
Rounded with high degree of polish.
Larger weight increase 30-50% due to coating material.
Logo or ‘break lines’ are possible.

Process
Difficult to automated e.g. traditional coating pan.
Considerable training operation required.
Multistage process.
Not able to be used for controlled release apart from enteric coating.

Example of sugar coated tablets

Brufen® POM

Available in 200mg and 400mg strength

Premarin® POM

Conjugated estrogens 625mcg (maroon) and 1.25mcg (yellow)

Simplified representation of sugar coating process-

2. Film coating
Modern approach to coating tablets, capsules, or pellets by surrounding them with a thin layer of
polymeric material.
Description of tablets: Shape dictated by contour of original core.
Process: Single stage process, which involves spraying a coating solution containing the following;
1. Polymer.
2. Solvent.
3. Plasticizer.

4. Colorant.
The solution is sprayed onto a rotating tablet bed followed by drying, which facilitates the removal of the
solvent leaving behind the deposition of thin film of coating materials around each tablet.

Advantages
Produce tablets in a single step process in relatively short period of time. Process enables functional coatings
to be incorporated into the dosage form.

Disadvantages
There are environmental and safety implications of using organic solvents as well as their financial expense.

Tablet appearance
Retains shape of original core.
Small weight increase of 2-3% due to coating material.
Logo or ‘break lines’ possible.

Process
Can be automated e.g. Accela Cota.
Easy training operation.
Single stage process.
Easily adaptable for controlled release allows for functional coatings.
Coating Material
a) Polymer used in film coating
Cellulose derivatives.
Methacrylate amino ester copolymers.

b) Plasticizer used in film coating

Polyols - Polyethylene glycol 400.
Organic esters - diethyl phthalate.
Oils/glycerides - fractional coconut oil.

c) Colorants used in film coating

Iron oxide pigments.
Titanium dioxide.
Aluminium lakes.

Water insoluble pigments are more favourable than water soluble colours for the following reasons:
Better chemically stability in light.
Optimised impermeability to water vapour.
Better opacity.
Better covering ability.

3. Press coating
Press coating process involves compaction of coating material around a preformed core. The technique
differs from sugar and film coating process.

Advantages
This coating process enables incompatible materials to be formulated together, such that one chemical or
more is placed in the core and the other (s) in the coating material.

Disadvantages
Formulation and processing of the coating layer requires some care and relative complexities of the
mechanism used in the compressing equipment.

4. Functional coatings
Functional coatings are coatings, which perform a pharmaceutical function.
These include;
a) Enteric coating -
The pH status of enteric coated polymers in the stomach
The ideal properties of enteric coated material
b) Controlled release coating
a) Enteric coating
The technique involved in enteric coating is protection of the tablet core from disintegration in the acidic
environment of the stomach by employing pH sensitive polymer, which swell or soluble in response to an
increase in pH to release the drug.

Aims of Enteric protection:

To mask taste or odour.
Protection of active ingredients, from the acidic environment of the stomach.
Protection from local irritation of the stomach mucosa.
Release of active ingredient in specific target area within gastrointestinal tract.

Examples of enteric coated OTC products

Enteric coated aspirin E.g. Micropirin® 75mg EC tablets

The pH status of enteric coated polymers in the stomach

The polymers used for enteric coatings remain unionise at low pH, and therefore remain insoluble. As the
pH increases in the gastrointestinal tract the acidic functional groups are capable of ionisation, and the
polymer swells or becomes soluble in the intestinal fluid.
Thus, an enteric polymeric film coating allows the coated solid to pass intact through the stomach to the
small intestine, where the drug is then released for absorption through the intestinal mucosa into the human
body where it can exert its pharmacologic effects.

The ideal properties of enteric coated material

Permeable to intestinal fluid.
Compatibility with coating solution and drug.
Formation of continuous film.
Nontoxic.
Cheap and ease of application.
Ability to be readily printed.
Resistance to gastric fluids.
Summary of Polymers used in pharmaceutical formulations as coating materials.

Polymer Trade name Application

Shellac EmCoat 120 N Enteric Coatings

Taste/Odor Masking
Marcoat 125

Cellulose acetate Aquacoat CPD® Enteric Coatings

Taste masking
Sepifilm™ LP Sustained release coating
Klucel® Sub coat moisture and
Aquacoat® ECD barrier sealant pellet
coating
Metolose®

Polyvinylacetate phthalate Sureteric® Enteric Coatings

Methacrylate Eudragit® Enteric Coatings

Sustained Release
Coatings
Taste Masking
Moisture protection
Rapidly disintegrating
Films

Polymer dissolution
Factors affecting the release of a drug from a polymer:
Thickness of the coating material,
pH,
Other excipients,
Ionic state,

Thickness of a coating material

To achieve enteric protection of the core 3-4 mg/cm2 of the polymer is required to be applied to the
dosage form.
Methacrylic acid copolymers require a lower amount of polymer compared to cellulose derivatives
which usually require higher amounts of polymer to achieve the same core protection as the former.
The more polymer layers that are applied the greater the rate of dissolution of the drug.

PH
Dissolution of polymers intended for enteric targeting is dependent upon the dissolution medium. This is
influenced by the composition of the polymer, the monomers, or the type and degree of substitution.
Ionic state
The rate of polymer dissolution is dependent upon the type of ions present in the dissolution
medium.
It was shown that sodium chloride prevented dissolution of some polymers.

Other excipients
Influence the dissolution of polymer.
Plasticizers may decrease or increase dissolution rate, depending on the nature of the plasticizer,
whether it is lipophilic or hydrophilic.

Coating Problems
1. Picking /chipping.
2. Roughness.
3. Sticking.
4. Film cracking/peeling.

Coating Equipment

Standard coating pans (Accela Cota).

Perforated coating pan.
Fluidized (air suspension) coater
Accela Cota
 Some common problems in tabletting
1. Weight fluctuation:

REASON REMEDY

Unsuitable granule size Change the granule size; usually small granules are for
smaller tablets.
Granule shape Prepare as round granules as possible to avoid uneven
air spaces.
Powder content The proportion of the fine powder should be kept
below 20% of granulate.
Volume differential The filling volume in the die should be near as
possible to the loose volume density.
Flow Control Lubricants- Choice and quantity may be changed to
control the flow of granules usually 1-5% are
sufficient.
Electrostatic charging This can be eliminated by spraying the granules with
water in order to increase their conductivity so that the
electricity is conducted t0 the surrounding machine
parts and earthed.

Humidity If the granulate is too wet Re-dry the granules.

2. Double feed:
Double feed may occur when tablets adhere to the punches or if they are not properly ejected due to
incorrect due to incorrect setting of ejectors check the setting of ejectors.
3. Mottling:
Mottling is an unequal distribution of color on a tablet, with light or dark areas standing an otherwise
uniform surface. One cause of mottling is a drug whose color differs from the tablet excipients or a drug
whose degradation products are colored. The use of colorants may solve the above problem.

4. Capping:
In capping the top or bottom part of the tablet separates from the main body completely are partially.

5. Sticking:
Adherence of granules to die walls is referred to as ‘sticking’

Excessive humidity Dry the granules and or air condition the room.

Low melting point of individual ingredient Separately granulate such ingredients.

Insufficient cohesion Slowly raise the compression pressure

Excess powders Sift out excess powders

Insufficient lubrication Increase or change the lubricant

Dies and punches dull Polish the dies and punches.

Defective engraving design Use rounded edges.

Evaluation of tablets:-

1. Appearance,
2. Content of active ingredient in the tablets,
3. Uniformity of weight,
4. Size and shape,
5. Organoleptic properties,
6. Uniformity content,
7. Hardness and friability test,
8. Disintegration test,
9. Dissolution,
 U.P.D.P.L.Product list (Tablets)

S.N. Tablets

1 Aspirin Tablets IP 300 mg

2 Ascorbic acid Tablets I.P. 500 mg

3 Calcium Lactate Tablets IP 300 mg

4 Chlorpheniramine Maleate Tablets IP 4 mg

5 Ciprofloxacin HCl Tablets IP 250 & 500 mg

6 Metronidazole 200 & 400 Tablets IP mg

7 Diclofenac Sodium Tablets IP 50 mg

8 Diethyl Carbamazine Citrate Tablets IP 50 mg

9 Diazepam Tablets IP 5 mg

10 Furazolidone Tablets IP 100 mg

11 Ibuprofen Tablets IP 200 & 400 mg

12 Fluconazole Tablets IP 150 mg

13 Mebendazole Tablets IP 100,200 mg

14 Roxithromycin Tablets IP 150 mg

15 Albendazole Tablets IP 400 mg

 CAPSULE SECTION
Capsule
Capsule is solid dosage forms in which one or more medicinal and or inert substances are enclosed within a
small shell or container generally prepared from a suitable form of gelatin. Depending upon their
formulation, the gelatin capsule shells may be hard or soft.

Characteristics:
1. May be swallowed whole by the patient.
2. May be inserted into the rectum for drug release and absorption from the site.
3. The contents may be removed from the gelatin shell and employed as a pre measured medicinal
powder, the capsule shell being use to contain a dose of the medicinal substance.
4. Elegance.
5. Ease of use.
6. Portability.
7. Tasteless shell to mask the unpleasant taste/odor of the drug.
8. Permits physician to prescribe the exact medication needed by the patient.
9. Conveniently carried.
10. Readily identified.
11. Easily taken.
12. tasteless when swallowed.
13. Commonly embossed or imprinted on their surface the manufacturer’s name and product code readily
identified.

Components of Capsules
1. Gelatin.
2. FD & C and D & C colorant.
3. Sugar.
4. Water - 12 to 16 % but may vary depending on the storage condition.
5. Sulfur dioxide (.15%) - prevent decomposition during manufacture.
6. Opaquants/Opacifying agent - titanium dioxide.

Type of capsule
The two main types of capsules are-
1. Soft Gelatin or Soft Gel Capsule
2. Hard Gelatin Capsule
1-Soft gel encapsulation

Cod liver oil soft gel capsules.

In 1834, Mothes and Dublanc were granted a patent for a method to produce a single-piece gelatin capsule
that was sealed with a drop of gelatin solution. They used individual iron moulds for their process, filling the
capsules individually with a medicine dropper. Later on, methods were developed that used sets of plates
with pockets to form the capsules. Although some companies still use this method, the equipment is not
produced commercially any more. All modern soft-gel encapsulation uses variations of a process developed
by R.P. Scherer in 1933. His innovation was to use a rotary die to produce the capsules, with the filling
taking place by blow molding. This method reduced wastage, and was the first process to yield capsules
with highly repeatable dosage.

2. HARD GELATIN CAPSULES

Two-part hard gelatin capsule

Also referred to as “DFC” Dry Filled Capsule. Manufactured into two sections, the capsule body and a
shorter cap.
A recent innovation in capsule shell design is the Snap-Fit, Coni-Snap, and Coni Snap Supro hard gelatin
capsules.
Capsule size

Empty Hard Gelatin Capsule Physical Specifications

Height or
Typical Fill Weights
Outer Locked Actual Vol.
Size (mg) 0.70
Diameter (mm) Length (mL)
Powder Density
(mm)

000 9.91 26.14 1.37 960

00 8.53 23.30 0.95 665

0 7.65 21.70 0.68 475

1 6.91 19.40 0.50 350

2 6.35 18.00 0.37 260

3 5.82 15.90 0.30 210

4 5.31 14.30 0.21 145

5 4.91 11.10 0.13 90

For human use, empty capsules ranging in size from 000 the largest to 5 the smallest. Generally, hard gelatin
capsule are used to encapsulate between 65 mg to 1 gram.

Characteristic
Usually use in the extemporaneous compounding of Rx.
Made of gelatin, sugar, and water.
Clear, colorless and essentially tasteless.
Colored with various FD & C and D & C dyes and made opaque by adding agents such as titanium
dioxide.
 Combination of colorants and Opaquants to make them distinctive, many with caps and bodies of
different colors.

Plasticizers:-

The amount of plasticizers used to make the capsule to hard or soft.

The plasticizers are used – Glycerin, Sorbitol.
Preservatives:-

If included, is generally a mixture of Methylparaben (4part) and Propylparaben (1part) to the

extent of 0.2%.
Flavors:-

If added, should not exceed 2%.

Generally the flavors are used- Ethyl vanillin or essential oils.
Sugar:-

If included, may be up to 5% to give the gelatin shell desirable chewable characteristics.

Additives:-

a) Diluents:-
The diluents have to be added to bring the medicament up to a desired bulk.
The quantities of diluents are related to the dose of the medicament and the capsule size.
b) Protective sorbents:-
Sometimes some inert materials are included to prevent the absorption of moisture by hygroscopic
substances.
Materials like – oxides and carbonates of Mg or Ca.
c) Glidants:-
Glidants become essential when the powders are filled by automated machinery requiring their
regular flow in the capsule bodies.
Glidants like- Talc, Stearates.
d) Anti-dusting compounds:-
These are the compounds which prevent the flow of dust particle of the drug in the air to causes
health hazards.
Anti-dusting compounds like- inert edible oils.
Gelatin
It is obtained by the partial hydrolysis of collagen obtained from skin, white connective tissue and
bones of animals.
Available in the form of a fine powder, a coarse powder, shreds, flakes, or sheets.
Stable in air when dry but when become moist - subject to microbial decomposition.
 HGC contain 13 to 16 % of moisture.
Extreme dryness- capsules may become brittle and crumble.

Manufacture of Hard Gelatin Capsule

Manufactured into 2 sections, the capsule body and the shorter cap.
The 2 parts overlap when joined, with the cap fitting snugly over the open end of the capsule
body.
Shells are produced by chemical dipping of pins or pegs of the desired shape and diameter into a
temperature-controlled reservoir of melted gelatin mixture.
The pegs made of manganese bronze, are affixed to plates, each capable of holding up to about 500
pegs.
Each plate is mechanically lowered to the gelatin bath, the peg submerge to the desired depth and
maintained for the desired period to achieve the proper length and thickness of coating.
The plate and the pegs are slowly lifted from the bath and the gelatin dried by a gentle flow of
temperature-and humidity-controlled air.
When dried, each capsule part is trimmed mechanically to the proper length and removed from the
pegs, the capsule bodies and caps are joined.

Capsules parameter as per I.P.

Product Dose Conversion (m.g.) Drug content Dissolution

(m.g.) (%) (%)
amoxicillin 250 285 90-110 80

Ampicilline 250 287 92.5-104.5 75

Trihydrate
Cephalexin 250 270 90-110 75
Monohydrate
Doxycycline 100 116 90-120 65

Rifampicine 150 165 92.5-107.5 70

Filling Hard Capsules Shells

1. Use Punch Method
powder is placed on a sheet of a clean paper or porcelain plate,
using spatula - formed into a cake having a depth of approximately one-fourth to one-third the
length of the capsule body,
then empty capsule body is held between the thumb and forefinger and punched vertically into the
powder cake repeatedly until filled,
2. Feton capsule filling
with empty capsule in the loader tray, the tray placed on top of the filler unit,
the loader inserts the capsules into the filling unit and is removed, and the top plate is lifted to
separate the caps from the bodies,
the powder is placed on the unit and the capsule bodies filled,
the top plate is returned to the unit and the caps placed on filled capsule bodies,
Process Capsule Filling
1. Milling /Sieving of all Ingredients.
2. Blending Powder Blender / Empty Capsules.
3. Capsule Filler.
4. Capsule cleaner.
5. Capsule injection screen.
6. Capsule check-weighing system/reject.
7. Finished capsules.
ProFill 100 - The ProFill 100 Capsule Filling Machine utilizes an advanced design for fool-proof manual
filling of two-piece capsules. With the ProFill 100 machine, there is no need for expensive capsule filling
equipment and electrical/vacuum connection.

Capsule Filling Machine:-

Semi-Automatic Capsule Filling Machine

Finishing:-

The filled the sealed capsules necessitate finishing operation before inspection, bowling or packing in strips
and labeling. The following steps are involve in the finishing process-

Pan polishing.
Cloth dusting.
Brushing.
Sealing.
Inspection (ROTOSORT).
Evaluation of capsules:-

1. Uniformity of weight.
2. Content of active ingredients in capsules.
3. Disintegration.
4. Dissolution.
 U.P.D.PL.Product list (Capsules & powder)

S.N. Capsules & Powder

1 Amoxycilline Trihydrate capsules IP 250 mg

2 Amoxycilline Trihydrate capsules IP 500 mg

3 Ampicilline Capsules IP 250 mg

4 Ampicilline Capsules IP 500 mg

5 Cephalexin Capsules IP 250 mg

6 Cephalexin Capsules IP 500 mg

7 Doxycycline Hydrochloride capsules IP 100 mg

8 Tetracycline capsules IP 250 mg

9 Tetracycline capsules IP 500 mg

10 Oral Réhydrations Salt citrate 270gm IP

 QUALITY CONTROL
Quality Assurance & Quality Control in Pharma Industry
QA: It is the sum total of the organized arrangements with the objective of ensuring that products will be
of the quality required for their intended use.

GMP: Is that part of Quality Assurance aimed at ensuring that products are consistently manufactured to
a quality appropriate to their intended use.

QC: Is that part of GMP concerned with sampling, specification & testing, documentation & release
procedures which ensure that the necessary & relevant tests are performed & the product is released for use
only after ascertaining its quality.

Quality Assurance (QA) Management Procedure:

1. How to write Standard Operating Procedure:
SOP describes standard SOP format that you can use immediately for your quality procedure.
SOP has instructions on how to write a formal operating procedure for your systems which your
people can follow every day.
2. Quality Documentation Management and Change Control:
This SOP describes how to generate new quality documents or change control of existing documents,
review of quality documents, satellite file management, and role of document author, approver,
document control officer and satellite file administrator.
3. Documentation Rule for GMP Documents:
This SOP describes the principles to be followed in GMP documents, entry of data and information,
signature requirements and correction technique of incorrectly entered data or information.
4. Quality Documentation-Control, Tracking and Distribution:
In this SOP you will find mainly the role of document control officer during the initiation, creation,
circulation and approval of new quality related documents.
It also describes the procedure of modification and review of existing document using a
documentation database.
Management of existing and superseded documents is also a part of this procedure.
You will see all the forms referred during the instruction are attached at the end of the procedure.
5. Shelf Life of Product:
This simple SOP describes the meaning of shelf life and provides on how to interpret shelf lives and
storage conditions for your raw materials from the Certificate of Analysis, determining expiry date
for your finished products by use of raw material date of manufacturing and their shelf lives.

Quality Control work (Summary)

Sampling of active pharmaceutical ingredients, Excipients, finished product & packing material etc.

1. Testing of API (Active Pharmaceutical Ingredients).

2. Testing of excipients.
3. Testing of sample process.
4. Testing of finished products.
5. Testing of packing material.
6. Stability studies of finished product.
7. Maintenance and calibration of instruments.
8. Procurement of chemicals and glass ware.
9. Procurement of reference standard.
10. Procurement of maintenance of clusters for microbiological testing.
11. To certificate analysis.
12. To study products complaints.
13. To destroy the control sample after six month of the date of expiry.
Quality control department

1. Quality control sampling section:

Responsibilities:-

To draw the sample of RM from store.

To draw the samples of F.G. from production department.
To keep control sample for reference & for stability studies.
Final inspection of each batch.
2. Quality control chemical section:
Responsibilities:-

Complete analysis of all RM/ process & F.G. sample as per prescribed standard.
To send report to production, store, Q C office.
To carry out stability testing etc.
Instrument maintenance and calibration.
3. Quality control microbiology section:
Responsibilities:-

Microbiological analysis of RM/process/FG/sample.

To send report to production, store, QC office.
Quality control packaging material test.
To carry out stability testing.
4. Quality control office:
Responsibilities:-

To make certificate of analysis of R.M. &finished products.

To maintain & keep records of analysis & certificate of analysis.
WORKING OF QUALITY CONTROL:-

VALIDATED SAMPLING SYSTEM

VALIDATED ANALYTICAL INSTRUMENT

ANALYTICAL VALIDATED METHOD

VALIDATED ANALYSIS

SUCCESSFUL ANALYSIS
List of quality control instruments:

S.NO NAME MAKE / MANUFACTURER

1 Tablet disintegration machine Campbell electronics

2 Water bath six hole thermostatic control JSGW

3 pH meter ECIL

4 Magnetic stirrer Reml

5 Friability test apparatus I. Equipment Cors

6 Vacuum pump Tempo

7 Oven SEW

8 B.O.D. JRSC

9 HPLC WATERS (INDIA)

10 Six stage dissolution rate test apparatus Tab machines

11 Melting point apparatus IEC& JSGW

12 Laminar flow Klenzald

13 Flame photometer Systronic

14 Digital balance ATCO

15 Spectrophotometer UV-1601(with CVT) Shaimadzu

Introduction

This the section essential for the quantitative & qualitative evolution of the raw material provided by
supplier , mixture material during processing & finished product evaluation supplied by chief manufacturing
chemist. Here also sample of finished batches are regularly checked for their validation. It consists of 3
sections-

1. Chemical section.
2. Instrumental section.
3. Micro-biological section.
1. Chemical section:-
In this section evaluation of drug, elemental analysis , mineral analysis, extraction, ignition, loss on
dying, melting point recording processing are carried out by following instruments:-

a) Test tubes, Boiling tubes, Pipette, Funnel, Beaker, Burette, Separating funnel: –
These are made up of borosilicate glass.
Pipettes are available from 1.50 ml.
Ammonia distillation test apparatus, boiling point apparatus are also available.
Separating funnels are from 250-500 ml.

(A) Burette. (B) Pipette (C) Separating funnel

b) Magnetic stirrer:-
Use to dissolve the sample; they have also temperature control along with stirrer speed set up.
 Magnetic stirrer

c) Kipp’s apparatus:-
Used ferrous sulphide with sulphuric acid to prepare hydrogen sulphide used for elemental analysis.

Kipp’s apparatus

d) Elemental water bath:-

For gradual heating from 30-100 C.

e) Melting point detector:-

Reads up to 500 C and is automatic electric heater melting is observed through a lenses.

Melting point detector

f) Muffle Furness:-
Consist of a steel body in which ¾ ft. thickness is coated by silica brick and glass wool may heat up to 1000
C. it can have coarse and fine temperature set up along with temperature increase rate controller.

Muffle Furness

g) Vacuum oven.
It is also a cubic steel container like simple oven but have a well lockable air tight- though with a glass
window in it.
It is attached with pressure gauze that reads 0-760 mmHg Vacuum.
There are two outlets one of which is attached to the Vacuum pump and other is open both are associated
with locks.
Whenever Vacuum is to be created door is close followed by locking the open outlet. Vacuum outlet is
opened and suction motor is start when Vacuum is created up to desired value Vacuum lock is also close
and Vacuum remains maintained up to the need.
Before opening the door lock of open, outlet is open to suck the air in the oven.
 It is used to determine the loss on drying of the drugs.
Example- vitamin- B2- 5- Phosphates.

Vacuum Oven

h) Reagent used in analysis – acid, base.

Acids. e.g. - Sulphuric acid, HCl, Nitric acid etc.
Bases. e.g. - NaOH, KOH etc.
Others e.g. – Distilled water, alcohol, Chloroform, Acetone, carbon tetrachloride, Benzene Pyridine etc.
Salts e.g. – Ammonium chloride, Na EDTA, Sodium acetate, calcium chloride etc.
Gases. e.g. – Hydrogen Sulphide
2. Instrumental section:-
In this section quantitative analysis of drugs, drug release extent specific rotation moisture content
determination, TLC spot study, colony counting, bone of inhabitation determination etc. processes are
carried out with following instrument-

a) Electronic Balance
For the weight variation testing of solid dosage form we randomly collect
10-20 tablets and weighting it and determine average weight of the each tablets. It should not be less than
90% of the required weight and not more than 110%.

Electrical Balance
 Weighing range is 1-100 mg.
Tolerance limit +0.01 mg.
It is used to weighing accurately the drug in small amount.
b) Friability tester:
This test is done for the knowing the amount of tablet is loss during the transportation by the friction with
the packing or during the manufacturing process.
The friability for tablet is not more or less than 10% of the actual weight.

Friability tester

c) Hardness tester:
Hardness is the main factor which effects the disintegration & dissolution time.
For the hardness testing generally hardness tester is used.

Model CTHT

capacity 20 Kgs.

Max. Tablet Dia. 25 mm

Net weight (Approx.) 1 Kg.

Gross weight (Approx.) 2.2 Kgs.

Machine Dimensions 410 (L) x 680 (B)

Case Dimension 30.5 (L) x 25.5 (B) x 7.5 (H)

 Tablet hardness tester: Pfizer type

d) UV-Spectrophotometer:
Infrared spectroscopy is one of the most powerful techniques of chemical identification. The infrared region
of the electromagnetic spectrum may be divided into three main sections:-
a) Newer infrared
b) Middle infrared
c) Far infrared
The main region of interest for analytical purposes is from 2.5 to 25 um i.e. 4000 to 400cm-1 lr spectra
originate from the different modes of variation and rotation of a molecules at wave length bellow 25 um the
radiation has sufficient energy to caves changes in the variation energy level of the molecules and these are
accompanied by change rotational energy level.

Spectrophotometer

e) Digital pH meter:
It is a device that consists of a glass electrode with very sensitive glass membrane that changes the
potential rapidly with variation in H+ ion concentration in the dipping solution.
This change in the potential recorded by recorder and is transformed in the form of pH.
 The instrument is calibrated at pH=4 (Potassium hydrogen phthalate buffer), pH=7 (Citro phosphate
buffer), pH-9.2 (Borax buffer). It has a tolerance limit of +0.05 (pH).

Digital pH Meter

Drugs pH Range

Ophthalmic solution 4-7.5

Liquid oral 4-8.5

Nikon 7-7.5

Niradex-N 7 Ophthalmic

Meeth 4

Bivite 4-5.5

Espilet-12 5-5.5 Oral

Metronidazole 5-5.5

Suspension

Bio-gel-A 8.5

f) Dissolution test apparatus:

Drugs released from the capsules are sometimes suspension in dissolution media is estimated with this
instrument.
At least 70% of the drugs should be released in 45 min.
Example- Amoxicillin (water medium), Piroxicam (Dissolution media of pH- 6.5 Phosphate Buffer).
 Dissolution Test Apparatus

h) Disintegration apparatus:-

For the drugs like sionate capsule (B-complex), Amiclox (Ampicilline & Cloxacillin), cephalic (folic
acid & ferrous sulphate), follifer (Ferrous fumerate & folic acid, vitamin – B12) etc.
Dissolution test are not specified in standard book hence disintegration test is carried out.
Water is used only as dissolution media.
To pass this test sample must dissolved within 15 min. without leaving any clot in the tube.

Disintegration Apparatus

i) Polarimeter:-
It is used for determine the purity, concentration and qualitative evaluation of drugs by determining the
specific rotation of the drug.
The drugs evaluated by this instrument are Chlorpheniramine, Ampicilline, and Amoxicillin etc.

Polarimeter
j) High Pressure Liquid Chromatography:

High Performance Liquid Chromatography

Apparatus:- A liquid chromatography consist of a reservoir containing the mobile phase a pump of force
the mobile phase throw the system at high pressure and injector to introduce the sample into the mobile
phase, chromatography column, detector, a data collection device.
Pumping system: - HPLC pumping system deliver major amount of mobile phase from the solvent
reservoirs to the column through the high pressure tubing and fitting.
Injector: - After dissolution in mobile phase is other suitable solution compounds to be chromatographer
are injected into the mobile phase either manually by syringe.
Columns: - For the most pharmaceuticals analysis separation is achieved by the partition of compounds in
the test solution between the mobile phase and stationary phase.
Detectors: - HPLC method requires the use of detectors such as consist of a flow through sale mounted at
the end of the column.
Data collection device: - Modern data station received and store dector output and print variables.

k) Karl –Fisher Titrator:-

It is completely automatic Titrator in which in closed beaker (supplied with dehumidified Nitrogen).
There is an automatic burette associated in which Karl- fisher reagent is filled by pumping.
After filling the sample, reagent is allow to drain when reagent is in excess indicator displays it and
when sample is excess indicator displays it at the end point another indicator displays the completion and
burette is automatically closed.
Moisture content is calculated in sample.
Karl- fisher reagent is use like - Dexamethasone Phosphate, Ciprofloxacin, Cephalexin, Cloxacillin, and
Ampicilline.
 Karl –fisher

l) UV-Light box:-
It is close box with door and a UV protective glass window fitted with an UV lamp & Visual lamp.
In this TLC chromatogram are observed in visual light range, upper UV range and lower UV range while
switching corresponding buttons respectively.

UV Light Box

3. Micro-biological section:-

a) Fumigation:-
This is a process to maintain asepsis in Lab.
500 ml of HCHO is mixed with 170 gm Potassium per magnate and is heated to vaporize.
During fumigation either of both solutions is heated in room after closing it completely for over a
night.
 So that intimation of vapors may occur with every corner and instrument.
Excess of HCHO is removed by soaking in Ammonia solution.
After fumigation wipening of instruments and wall in carried out with 70% Isopropyl alcohol, this
maintains asepsis for a long time.
b) Auto-clave:-
Autoclave is the apparatus used to sterilize with pressurized steam,
The autoclave is an essential unit of every microbiology laboratory,
An autoclave is usually operated at a pressure of 15 lb in2, at which temperature of pure steam is
121’C.
The length of time depends on the material which is sterilized.

Auto Clave

c) Laminar flow bench –

It is device in which a septic handling, transferring, filling etc. processes are carried out.
Consist of a HEPA Filter (Pole size 0.2µm) through which microbial free air is blown that prevents
the contamination of the area from microbes.
Before processing UV-light is set on area is allowed to sterilized than UV-light is set of windows
are open (HEPA-filters remain on) and working is started.
Whenever working is stop UV-light again set on to maintain the area sterile.
It is used mostly for aseptic transfer of culture media to the petridishes and test tube and also in
micro manipulation processes.

Laminar flow bench

d) Hot air oven –

Hot air oven

Hot air ovens are electrical devices used in sterilization.
The oven uses dry heat to sterilize.
They can be operated from 50 to 300 °C (122 to 572 °F).
There is a thermostat controlling the temperature.
The standard settings for a hot air oven are:

-1.5 to 2 hours at 160 °C (320 °F)

-6 to 12 minutes at 190 °C (374 °F)

e) B.O.D. Indicator:-
Used to provide suitable climatic condition like Temperature, Oxygen etc. to the growing microbes
in culture mediums in fully controlled way.
Used to incubate the culture for complete growth of microbes to develop colonies (about 10 days) it
is available in 50 liter & 200 liter capacity.

BOD Incubator

f) Hot Plate With Thermostat:-

It is used to dry and settle the Medias and petridishes are to store the culture mediums in microbial
free environment below 100º C for small times.
 Hot Plate with Thermostat

g) Compound microscope:-
Maximum magnification is up to 1000 times and is used for microbial manipulations.

Compound Microscope

h) Membrane filter:-

Membrane Filter
 It is cellulose acetate / phthalate etc. derived circular pad of 100-150 µm thickness, 45 mm diameter
& 0.45 mm pore size.
Fitted in a steel holder supported by a steel strainer and used to check the microbial contamination in
fluids.
Ophthalmic water is passed through filter under Vacuum and the filter disc is divided in 4 parts
aseptically in Laminar Flow Bench. Two of which are transferred to fluid Thioglycolate media and
rests are transferred to casein digest media. (For aerobic and non-aerobic Bacteria) and are incubated
in B.O.D. for 7 days.
Any kind of microbial growth shows microbial contamination of the fluid.
i) Microbial colony counter:-
Plate counting machine consist of a base plate printed with squares over which magnifying lenses is
present a touch counter electronic pen is used to count the colony that get displayed on the screen.
It is used for counting microbial colonies, Solid Agar Culture Media incubated for the validation
sterile area water containers of ophthalmic section filter membranes & autoclaves.

Microbial Colony Counter

j) Zone Of Inhibition Reader:-

Consist of a Petridis holder that moves over a plate form below a reflector assembly.
Whenever diameter of Z.O.I is to be measured the Petridis is placed in the holder and a prism is
kept on the Z.O.I. in disc.
Assembly is moved below the reflector in such a way that adjustment makes the Z.O.I. visible from
the front.
The reading on the meter shows the Z.O.I. in mm.
Used to check the efficacy of antibiotics.

Digital Antibiotic Zone Reader

 PACKEGING SECTION

Packaging is the science, art and technology of enclosing or protecting products for distribution, storage,
sale, and use. Packaging also refers to the process of design, evaluation, and production of packages.
Package labeling or labeling is any written, electronic, or graphic communications on the packaging or on a
separate but associated label.

Types of packaging:
There are two types of packaging-

1. Primary packaging.
2. Secondary packaging.
1-PRIMARY PACKAGING:-

It is the packing which is in contact with medicament (capsule or tablet).

a) Blister packaging:-
• In this PVC and Al Foil is used for packaging.
• Sometimes Al foil is used wholly for packaging-
Thickness of Al foil = 0.025mm ± 10%.
Thickness of PVC = 0.25 mm ±10%.
• The blister package is formed by heat- softening a sheet of thermoplastic resin and vacuum drawing
the softened sheet of plastic into a contoured mold.
• Blister packaging machine consist of-
Feeder (vibrator).
A guide track.
A forming dies.
Forming heater.
Sealing heater.
Cutter.
Printing registration controller.

Blister Packaging

TEMPRATURE:-

Forming heater = 140º-170º C.

Sealing heater = 170º-200º C.
b) Strip packaging:-
The strip package is form by feeding to webs of a heat sealable flexible film through either a heated
crimping roller or a heated reciprocating platen. In this the product is drop into the pocket formed prior to
forming the final set of seals.

Machine:-

• It consist of –
Hopper.
Disc.
Channel (chute).
Two rollers (for Al foil).
Cutter (center cutter).
Conveyer belt.
Thermostat.
Selector.
• When primary (strip & blister) packaging is done. The strips & blisters are subject for secondary
packaging.

Strip Packaging

2-SECONDARY PACKAGING:-

It is the packaging which is in contact with the primary packaging.

It involved –

• Cartoons (printed).
• Corrugated boxes (CB).
• White board box.
• Corrugated boxes consist of 3 ply or 5 ply or 7 ply as per requirement.
• When secondary packaging is complete a BOPP tape (Bio Oriented Poly Propylene Tape) is use for
sticking.
The purposes of packaging and package labels
Packaging and package labeling have several objectives:

Physical protection - The objects enclosed in the package may require protection from, among other
things, shock, vibration, compression, temperature, etc.

Barrier protection - A barrier from oxygen, water vapor, dust, etc., is often required. Permeation is a
critical factor in design. Some packages contain desiccants or Oxygen absorbers to help extend shelf life.
Modified atmospheres or controlled atmospheres are also maintained in some food packages. Keeping the
contents clean, fresh, and safe for the intended shelf life is a primary function.

Containment or agglomeration - Small objects are typically grouped together in one package for
reasons of efficiency. For example, a single box of 1000 pencils requires less physical handling than 1000
single pencils. Liquids, powders, and granules need containment.

Information transmission - Packages and labels communicate how to use, transport, recycle, or
dispose of the package or product. With pharmaceuticals, food, medical, and chemical products, some types
of information are required by governments.

Marketing - The packaging and labels can be used by marketers to encourage potential buyers to
purchase the product. Package design has been an important and constantly evolving phenomenon for
several decades. Marketing communications and graphic design are applied to the surface of the package
and (in many cases) the point of sale display.

Convenience - Packages can have features which add convenience in distribution, handling, stacking,
display, sale, opening, reclosing, use, and reuse.

Portion control - Single serving or single dosage packaging has a precise amount of contents to control
usage. Bulk commodities (such as salt) can be divided into packages that are a more suitable size for
individual households. It is also aids the control of inventory: selling sealed one-liter-bottles of milk, rather
than having people bring their own bottles to fill themselves.

Packaging machines
A choice of packaging machinery includes, technical capabilities, labor requirements, worker safety,
maintainability, serviceability, reliability, ability to integrate into the packaging line, capital cost, flexibility
(change-over, materials, etc.), energy usage, quality of outgoing packages, qualifications (for food,
pharmaceuticals, etc.), throughput, efficiency, productivity,
 High speed conveyor with bar code scanner for sorting transport packages.

Label printer applicator applying a label to adjacent panels of a corrugated box.

Packaging machines may be of the following general types:

• Blister packs, skin packs and Vacuum Packaging Machines.
• Bottle caps equipment, Over-Capping, Lidding, Closing, Seaming and Sealing Machines.
• Cartooning Machines.
• Box, Case and Tray Forming, Packing, Unpacking, Closing and Sealing Machines.

• Cleaning, Sterilizing, Cooling and Drying Machines.

• Conveyors, Accumulating and Related Machines.
• Feeding, Orienting, Placing and Related Machines.
• Filling Machines: handling liquid and powdered products.
• Package Filling and Closing Machines.
• Form, Fill and Seal Machines.
• Inspecting, Detecting and Checkweigher Machines.
• Palletizing, Depalletizing, Unit load assembly.
• Product Identification: labeling, marking, etc.
• Wrapping Machines.
 CONLUSION

UPDPL helped us to imbibe the detailed information about tablet section, liquid section, capsule section &
packaging section.

This industrial training provided a valuable learning experience in the carrier exploration process and gave
us unexpected benefit. Now I have evaluated the class room taught facts and ideas and applied them to the
real life situation. We came to know about many things such as the GMP (Good Manufacturing Process),
the Current Good Manufacturing Process (CGMP).the basic laboratory requirement for product validation,
the variety of machine used in the large scale industries of medicine etc.

These and many other factors cause the enhance of my knowledge and have created a lifelong interest to
learning through an exposure to new educational experience
 REFRENCE
1. Tablet-
Pharmaceutics. The science of dosage forms design. (M.E. Aulton)
The theory and practice of industrial pharmacy.
Pharmaceutical dosage forms : Tablets. Volume 2.
Pharmaceutical dosage forms and drug delivery systems.
Pharmaceutical Manufacturing Handbook Production and Processes.
2. Coating
http://www.touchbriefings.com/pdf/17/pt031_p_rajabi_siahboomi.pdf
http://www.pharmpedia.com/Tablet:Tablet_coating#Aspects_of_tablet_coating
http://www.dipharmatech.com/pharmaceutical_technical_articles.html
http://www.roehm.com/en/pharmapolymers.html
3. Capsule-
L. Lachman, H.A. Lieberman, J.L. Kanig (1986). The Theory and Practice of Industrial Pharmacy
(Third Ed.). Lea & Fibiger, Philadelphia.
http://www.wikipedia.org.

4. Quality control-
Ashutosh kar, Pharmaceutical analysis, theory, methodology and drug assay, volume 2,
www.ich.org
www.fda.gov

WWW.PHARMANOTES.ORG