INDUSTRIAL TRAINING REPORT

PRAVESH MAURYA

1. R.K. Pharmacy College, Azamgarh Page 1

A PROJECT REPORT ON INDUSTRIAL
TRAINING
A Project Submitted
In Partial Fulfillment of the Requirements
For the Degree of
BACHELOR OF PHARMACY
By
PRAVESH MAURYA
(1623350034)
Under the Supervision of
Mrs. BHAVANA YADAV
Assistant Professor
DEPARTMENT OF PHARMACY

R. K. PHARMACY COLLEGE
(Sathion – Azamgarh,U.P.,276403)
Approved by AICTE, PCI and Affiliated to Dr. A.P.J. Abdul Kalam Technical
University, Lucknow, UP.
MAY 2019

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INDEX
Sr. No CONTENTS Page No.
1.0 Certificate 3
2.0
Declaration
4
3.0
Endorsement by guide
5
4.0
Endorsement by principal
6
5.0 Acknowledgement 7
6.0 Industry Profile 8
7.0 Granulation 10
8.1 Compression 14
9.2 Coating 20
10.3 Capsule 24
11.0 Hard gelatin capsule 25
12.1 Soft gelatin capsule 25
13.2 Packaging 27
14.0 GMP Requirements 31
15.0 Reference 32

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R. K. PHARMACY COLLEGE



CERTIFICATE
This is to certified that PRAVESH MAURYA has carried out the project work
entitled “Industrial Training”for the award of BACHELOR OF
PHARMACY From Dr. A.P.J. Abdul Kalam Technical University,
Lucknow ,under my supervision. This project report work and the studies
carried out by the student and the content of the report do not form the award of
any other degree to the candidate or to anybody else.



DIRECTOR SUPERVISOR
Dr. Anil Kumar Gangwar Mrs. BhavnaYadav
R.K. Pharmacy College, Assistant Professor
Azamgarh Deptt.Of Pharmacology
R. K. Pharmacy College

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Azamgarh

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R. K. PHARMACY COLLEGE








DECLARATION
I hereby declare that this project work entitled “INDUSTRIAL TRAINING REPORT”
Submitted to A.K.T.U. , Lucknow, is a bonafide and genuine work carried out by us under
the guidance of MS. BHAVNA YADAV. I also declare that the material entitled in it is
original and the same has not previously formed the basis for the award of any diploma,
degree association ship or fellowship of other university or institute.







PRAVESH MAURYA
(1623350034)
Date:

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R. K. PHARMACY COLLEGE





ENDORSEMENT BY THE GUIDE
This is certifying that the project entitled the study of “INDUSTRIAL TRAINING REPORT”
is a bonafide work done by PRAVESH MAURYA in a partial fulfillment of the requirement
of the degree of “Bachelor of pharmacy” of A.K.T.U. Lucknow.








Signature
MS. BHAVNA YADAV
Assistant Professor

Date:

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R. K. PHARMACY COLLEGE






ENDORSEMENT BY THE PRINCIPAL
This is certify that the project entitled the study of “INDUSTRIAL TRAINING REPORT” is
a bonafide work done by PRAVESH MAURYA in a partial fulfillment of the requirement of
the degree of “Bachelor of pharmacy” of A.K.T.U. Lucknow.







Signature
Dr. A.K. Gangwar
Principal
Date:

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ACKNOWLEDGMENT
I hereby express my profound and sincere gratitude towards the Management and Faculty
member of my institute for providing of all the facility support during my academics
dissertation report.
“Expression of feeling by words makes them less significant when it comes to makes
statement of gratitude.”
This project is a great achievement in my carrier and it is my privilege to acknowledge all
those in completing this project report.
I humbly owe the completion of this dissertation work to Almighty God and my parents.
I must thankful to Dr. A.K. Gangwar , Director , R.K. Pharmacy College, Azamgarh,for
giving me opportunity to show my ability to do something better .
I would like my deep sense of gratitude to Dr. Abhay Pratap Yadav , Mr.Rizwan Shahab,
Mr.Omkar Singh, Mr.Kamlesh Kumar Yadav , Miss. Shivanki Verma & Mr. Mohd Amir, for
their timely help and valuable suggestion it was difficult me to successfully complete this
project.
I express my sincere gratitude to Mrs. Bhavana Yadav and Miss. Asha Roshan for their
constant advices , suggestion and encouragement.
I am also highly thankful to Mr.Rohitashwa Yadav,Librarian for co-operation of this project.
For the really good atmosphere for their collegiality and for good collaboration –which is not
matter of course – my especially gratitude goes to all my friend for encouragement and
motivation “friends are candle in dark and I must fortunate one that this candle made
my way sparkled by their brilliance of light.”
Finally, I would like to express deep sense of gratitude to my Parents for their valuable co-
operation and affection all through the dissertation work.

PRAVESH MAURYA
1623350034
B.Pharm 3
rd
Year
6
th
Semester

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Industry Profile
About Industry

OLIVE HEALTHCARE
No A 4 ,Sara Industrial Estate ,Village Rampur Chakraia Ponta Sahib Rd. Dehradun,Uttarakhand,
India Tel [phone]

Olive healthcare is a fully integrated developer, manufacturer and marketer of broad range of
soft gelatin formulations with a strong regulatory and infrastructure back end to support its
r&d and growth strategy in global markets.
Olive exclusively develops and deals only with soft gelatin formulations over the last 4
decades and currently operates 3 state-of-the-art manufacturing sites in India with approvals
ranging from who GMP to US FDA and ISO certification for quality, environment and
occupational health and safety. Olive also stands approved by the eu health and sanitary
authority for exports to eu and allied nations.
Olive is the ideal of source of soft gelatin formulations from India the world due to
flexibilities with olive's business model, manufacturing capabilities in terms of low volume
and high volume requirements with strong technical support alongside the competitive edge
that it inherits by virtue of its sourcing and procurement strength for global markets.
VISION AND MISSION
Vision :
"To be a global pharmaceutical company with increasing focus on innovative
research and developed markets."
Mission :
"A Reliable source of Quality Healthcare products that safeguard Life and
Health over the world."
The business is focused around the delivery of three strategic priorities which
aim to increase growth, reduce risk and improve our long-term financial
performance. These priorities are: grow a balanced global business, deliver
more products of value, and simplify the operating model.

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To fulfill this goal, we seek to achieve excellence in:
 Dedicated Research and Development in the field of soft gels.
 Manufacturing expertise alongside a state-of-the-art facility.
 Maintenance of globally benchmarked quality and regulatory standards.
 Customer satisfaction through delivery of products and services with an organized approach.
 Creating and sustaining a professional environment conducive to learning and human
resource development.
CERTIFICATE OF INDUSTRIAL TRAINING

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GRANULATION
Definition:
The granulation process as ‘‘anyprocess whereby small particles are gathered into larger,
permanent masses in whichthe original particles can still be identified.’’ This definition is of
course particularlyappropriate to a pharmaceutical granulation where the rapid breakdown of
agglomerates is important to maximize the available surface area and aid in solution of
theactive drug. The granulation process of size enlargement used within the
pharmaceuticalindustry has its roots in ancient times. The practice of delivering medicinal
powderby hand rolling into a pill by using honey or sugar has been used for centuries.
It is still the practice to deliver the botanical and herbal extract in homeopathic andayurvedic
branches of medicine, which are still practiced in India along with allopathicmedicine. The
term ‘‘granulated’’ material is derived from the Latin word‘‘granulatum,’’ meaning grained.
The granulated material can be obtained by directsize enlargement of primary particles, or
size reduction from dry compacted material.
In modern times, granulation technology has been widely used by a wide rangeof industries,
such as coal, mining, and agrochemical. These industries employagglomeration techniques to
reduce dust, provide ease of handling, and enhancethe material’s ultimate utility.
The development of pharmaceutical granulation was driven by the invention ofthe tablet
press by W. Brockedon in 1843. Subsequent improvements in the tabletmachinery were
patented in the United States by J. A. Mc. Ferran (1874), T. J. Young(1874), and J. Dunton
(1876). The demands on the granulation properties were furtherenhanced in the 1970s as
high-speed tablet and capsule filling machines with automatedcontrols were introduced. The
continuous refinements in the regulatory requirementssuch as low-dose products requiring
blend uniformity/content uniformitynecessitated knowledge and technology to produce the
required granule characteristics.
The high-speed compression and capsule filling machines require a uniform flow of material
to the dies or filling stations that produce pharmaceutical dosage form.
Granulation is an example of particle design. The desired attributes of thegranule are
controlled by a combination of the formulation and the process.
Granulation methods can be divided into two major types: wet methods whichutilize some
form of liquid to bind the primary particles, and dry methods which donot utilize any liquid

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1-Receve the raw material As BMR from Raw material store
2-Shiting of raw material (API & EPI) in vibro shifter


Vibro shifter

Wet granulation:
Wet granulation is a process of using a liquid binder to lightly agglomerate the powder
mixture. The amount of liquid has to be properly controlled, as over-wetting will cause the
granules to be too hard and under-wetting will cause them to be too soft and friable. Aqueous

Paste kettle Rapid mixer granulator
Solutions have the advantage of being safer to deal with than solvent-based systems but may
not be suitable for drugs which are degraded by hydrolysis.

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Procedure:
1. The active ingredient and excipients are weighed and mixed.
2. The wet granulate is prepared by adding the liquid binder–adhesive to the powder
blend and mixing thoroughly. Examples of binders/adhesives include aqueous
preparations of cornstarch, natural gums such as acacia, cellulose derivatives such as
methyl cellulose, gelatin and poidvone.
3. Screening the damp mass through a mesh to form pellets or granules.
4. Drying the granulation. A conventional tray-dryer or fluid-bed dryer are most
commonly used.
5. After the granules are dried, they are passed through a screen of smaller size than the
one used for the wet mass to create granules of uniform size.
Low shear wet granulation processes use very simple mixing equipment, and can take a
considerable time to achieve a uniformly mixed state. High shear wet granulation processes
use equipment that mixes the powder and liquid at a very fast rate, and thus speeds up the
manufacturing process. Fluid bed granulation is a multiple-step wet granulation process
performed in the same vessel to pre-heat, granulate, and dry the powders. It is used because it
allows close control of the granulation process.
Dry granulation:
Dry granulation processes create granules by light compaction of the powder blend under low
pressures. The compacts so-formed are broken up gently to produce granules (agglomerates).
This process is often used when the product to be granulated is sensitive to moisture and heat.
Dry granulation can be conducted on a tablet press using slugging tooling or on a roll press



Fluid bed dryer

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Called a roller compactor. Dry granulation equipment offers a wide range of pressures
to attain proper densification and granule formation. Dry granulation is simpler than
wet granulation, therefore the cost is reduced. However, dry granulation often
produces a higher percentage of fine granules, which can compromise the quality or
create yield problems for the tablet. Dry granulation requires drugs or excipients with
cohesive properties, and a 'dry binder' may need to be added to the formulation to
facilitate the formation of granules.

Granule lubrication:
After granulation, a final lubrication step is used to ensure that the tabletting blend does not
stick to the equipment during the tablet process. This usually involves low shear blending of
the granules with a powdered lubricant, such as magnesiumstearate or stearicacid.


Octagonal Blander

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COMPRESSION
In the tablet compressing process, the main guideline is to ensure that the appropriate amount
of active ingredient is in each tablet. Hence, all the ingredients should be well-mixed. If a
sufficiently homogenous mix of the components cannot be obtained with simple blending
processes, the ingredients must be granulated prior to compression to assure an even
distribution of the active compound in the final tablet. Two basic techniques are used to
granulate powders for compression into a tablet: wet granulation and dry granulation.
Powders that can be mixed well do not require granulation and can be compressed into tablets
through direct compression.



Tablets that failed due to capping and lamination compared to a normal tablet
Whatever process is used to make the tablet blend, the process of making a tablet by powder
compaction is very similar. First, the powder is filled into the die from above. The mass of
powder is determined by the position of the lower punch in the die, the cross-sectional area of
the die, and the powder density. At this stage, adjustments to the tablet weight are normally
made by repositioning the lower punch. After die filling, the upper punch is lowered into the
die and the powder is un axially compressed to a porosity of between 5 and 20%. The
compression can take place in one or two stages (main compression, and, sometimes, pre-
compression or tamping) and for commercial production occurs very fast (500–50 ms per
tablet). Finally, the upper punch is pulled up and out of the die (decompression), and the
tablet is ejected from the die by lifting the lower punch until its upper surface is flush with the
top face of the die. This process is repeated for each tablet.
Common problems encountered during tablet manufacturing operations include:
 Fluctuations in tablet weight, usually caused by uneven powder flow into the die due to
poor powder flow properties.

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 Fluctuations in dosage of the Active Pharmaceutical Ingredient, caused by uneven
distribution of the API in the tabletting blend (either due to poor mixing or separation in
process).
 Sticking of the powder blend to the tablet tooling, due to inadequate lubrication, worn or
dirty tooling, or a sticky powder formulation
 Capping, lamination or chipping. This is caused by air being compressed with the tablet
formulation and then expanding when the punch is released: if this breaks the tablet apart,
it can be due to incorrect machine settings, or due to incorrect formulation: either because
the tablet formulation is too brittle or not adhesive enough, or because the powder being
fed to the tablet press contains too much air (has too low bulk density).
 Capping can also occur due to high moisture content.
Tablet compaction machine:
Tablets are made by compressing a formulation containing a drug or drugs with excipients on
stamping machine called presses. Tablet presses are designed with following basic
components:
1) Hopper for holding and feeding granulation
2) Dies that define the size and shape of the tablet.
3) Punches for compressing the granulation within the dies.
4) Cam tracks for guiding the movement of the punches.
5) A feeding mechanism for moving granulation from hopper into the
Dies
Tablet formulations are designed and tested using a laboratory machine called a Tablet
Compaction Simulator or Powder Compaction Simulator. This is a computer controlled
device that can measure the punch positions, punch pressures, friction forces, die wall
pressures, and sometimes the tablet internal temperature during the compaction event.
Numerous experiments with small quantities of different mixtures can be performed to
optimize a formulation. Mathematically corrected punch motions can be programmed to
simulate any type and model of production tablet press. Initial quantities of active
pharmaceutical ingredients are very expensive to produce, and using a Compaction Simulator
reduces the amount of powder required for product development.

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Tablet pressing:

Tablet pressing operations


Accura press IV Rotary tablet press

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Tablet press, also called tablet machines, range from small, inexpensive bench-top models
that make one tablet at a time (single-station presses), with only around a half-ton pressure, to
large, computerized, industrial models (multi-station rotary presses) that can make hundreds
of thousands to millions of tablets an hour with much greater pressure. The tablet press is an
essential piece of machinery for any pharmaceutical and nutraceutical manufacturer.
Common manufacturers of tablet presses include Stokes, Fette Compacting, Korsch, Kikusui,
Manesty, B&D, PTK, IMA and Courtoy. Tablet presses must allow the operator to adjust the
position of the lower and upper punches accurately, so that the tablet weight, thickness and
density can each be controlled. This is achieved using a series of cams, rollers, and/or tracks
that act on the tablet tooling (punches). Mechanical systems are also incorporated for die
filling, and for ejecting and removing the tablets from the press after compression.
Pharmaceutical tablet presses are required to be easy to clean and quick to reconfigure with
different tooling, because they are usually used to manufacture many different products.
There are 2 main standards of tablet tooling used in pharmaceutical industry: American
standard ‘TSM’ and European standard ‘EU’. TSM and EU configurations are similar to each
other but cannot be interchanged.

Production:
Tablets are obtained by compression of uniform volumes of powders or granules by applying
high pressures and using punches and dies. The particles to be compressed consist of one or
more medicaments, with or without auxiliary substances such as diluents, binders,
disintegrating agents, lubricants, glidants, permitted colours and substances capable of
modifying the behavior of the medicaments in the digestive tract. Such substances must be
innocuous and therapeutically inert in the quantities present. In the production of tablets,
measures are taken to ensure that they have sufficient strength to avoid crumbling or breaking
on handling or subsequent handling. Chewing tablets are manufactured to ensure that they are
easily crushed by chewing. During manufacture, packaging, storage and distribution of
tablets, suitable means shall be taken to ensure their microbial quality.

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Test:
Uniformity of container contents:
Tablets comply with the test for contents of packaged dosage forms.
Content of active ingredients:
Determine the amount of active ingredients by the method described in the Assay and
calculate the amount of active ingredients per tablet. The result lies within the range for the
content of active ingredients stated in the monograph. This range is based on the requirement
that 20 tablets, or such other number as may be indicated in the monograph, are used in the
Assay. Where 20 tablets cannot be obtained, a smaller number, which must not be less than 5,
may be used, but to allow for sampling errors the tolerances are widened. The requirements
of Table 1 apply when the stated limits are between 90 and 110 per cent. For limits other than
90 to 110 per cent, proportionately smaller or larger allowances should be made.
Uniformity of content:
This test is applicable to tablets that contain 10 mg or less than 10 mg or less than 10 per cent
w/w of active ingredient. For tablets containing more than one active ingredient carry out the
test for each active ingredient that corresponds to the aforementioned conditions. The test is
also applicable to coated tablets other than film coated tablets, irrespective of their content of
active substances. The test for Uniformity of content should be carried out only after the
content of active ingredients in a pooled sample of the tablets has been shown to be within
accepted limits of the stated content. The test for Uniformity of content is not applicable to
tablets containing multivitamins and trace elements.
Uniformity of weight:
This test is not applicable to coated tablets other than film-coated tablets and to tablets that
are required to comply with the test for uniformity of content for all active ingredients.
Dissolution:
Where required, the requirements for this test are given in the individual monographs. Where
a dissolution test is prescribed, the disintegration test may not be necessary.
Disintegration:
Use water as the liquid. Add a disc to each tube. Operate the apparatus for 15 minutes, unless
otherwise stated in the individual monograph. Examine the state of the tablets. If the tablets
fail to comply because of adherence to the discs, repeat the test on a further 6 tablets omitting
the discs. The tablets comply with the test if all 6 tablets have disintegrated.
The test does not apply to chewable tablets.
Disintegration:
For coated tablets other than film coated tablets.
Use water as the liquid. Add a disc to each tube. Operate the apparatus for 60 minutes, unless
otherwise stated in the individual monograph. Examine the state of the tablets. If any of the
tablets has not disintegrated, repeat the test on a further 6 tablets, replacing water with 0.1 M
hydrochloric acid. The tablets comply with the test if all 6 tablets have disintegrated in the
acid medium.
Determine at 24ºC to 26ºC and operate the apparatus for 3 minutes.

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COATING
Tablet coatings perform one or more of the following functions. They may: mask the taste of
unpalatable drugs, protect the drug from deterioration due to light, oxygen or moisture,
separate in compatible ingredients, control the release of medicament in the gastro intestinal
tract, and provide an elegant or distinctive finish to the tablet.
The materials used for coating may largely comprise sucrose (sugar coating), water‐soluble
film‐forming polymers (film coating) or substances which are soluble in the intestinal
secretions but not in those of the stomach (enteric coating). These types of coating can all be
applied by the pan or auto-coater; the compression coating technique is suitable for sugar and
enteric coatings, but not for film coating.
Types of Coating:
Different coating processes are: Pan coating (conventional coating), auto coating (auto
coater).
Pan coating:

PAN COATING AUTO COATER

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Evaluation of Tablet:

1. General Appearance:
The general appearance of a tablet, its identity and general elegance is essential for consumer
acceptance, for control of Lot‐to‐lot uniformity and tablet‐to‐tablet uniformity. The control of
general appearance involves the measurement of size, shape, color, presence or absence of
odour, taste etc.
2.Size & Shape:
It can be dimensionally described & controlled. The thickness of a tablet is only variables.
Tablet thickenss can be measured by micrometer or by other device. Tablet thickness should
be controlled within a ±5% variation of standard value.
3. Unique identification marking:
These marking utilize some form of embossing, engraving or printing. These markings
include company name or symbol, product code, product name etc.
4.Organoleptic properties:
Colour distribution must be uniform with no mottling. For visual colour comparison compare
the colour of sample against standard colour.
5. Hardness and Friability:
Tablet requires a certain amount of strength or hardness and resistance to friability to with
stand mechanical shakes of handling in manufacture, packaging and shipping








Monsanto tester Pfizer Hardness Tester

6. Friability:
Friability of a tablet can determine in laboratory by Roche friabilator. This consist of a plastic
chamber that revolves at 25 rpm, dropping the tablets through a Distance of six inches in the
friabilator, which is then operate for 100 revolutions. The tablets are reweighed. Compress
tablet that lose less than 0.5 to 1.0% of the Tablet weigh are consider acceptable.

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Friability Test Apparatus

2. Drug Content and Release:
(I)Weight Variation test (U.S.P.):
Take 20 tablets and weighed individually. Calculate average weight and compare the
individual tablet weight to the average. The tablet pass the U.S.P. test if no more that 2 tablets
are outside the percentage limit and if no tablet differs by more than 2 times the percentage
limit.
(II)Content Uniformity Test:
Randomly select 30 tablets. 10 of these assayed individually. The Tablet pass the test if 9 of
the 10 tablets must contain not less than 85% of the labeled drug content and the 10
th
tablet
may not contain less than 75% and more than 125% of the labeled content. If these conditions
are not met, remaining 20 tablets assayed individually and none may fall outside of the 85 to
115% range.

(III)Disintegration Test (U.S.P.):
The U.S.P. device to test disintegration uses 6 glass tubes that are 3” long; open at the top and
10 mesh screens at the bottom end. To test for disintegration time, one tablet is placed in each
tubeand the basket rack is positioned in a 1‐L beaker of water, simulated gastric fluid or
simulated intestinal fluid at 37±2 ºC such that the tablet remain 2.5 cm below the surface of
liquid on their upward movement and not closer than 2.5 cm from the bottom of the beaker in
their downward movement. Movethe basket containing the tablets up and down through a
distance of 5‐6 cm at a frequency of 28 to 32 cycles per minute. Floating of the tablets can be
prevented by placing perforated plastic discs on each tablet.
According to the test the tablet must disintegrate and all particles must pass through the 10
mesh screen in the time specified. If any residue remains, It must have a soft mass.
Disintegration time:
Uncoated tablet: 5‐30 minutes
Coated tablet: 1‐2 hours

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3. Dissolution Test (U.S.P.):
Two set of apparatus:
Apparatus‐1:
A single tablet is placed in a small wire mesh basket attached to the bottom of the shaft
connected to a variable speed motor. The basket is immersed in a dissolution medium (as
specified in monograph) contained in a 100 ml flask. The flask is cylindrical with a
hemispherical bottom. The flask is maintained at 37±0.5ºC by a constant temperature bath.
The motor is adjusted to turn at the specified speed and sample of the fluid are withdrawn at
intervals to determine the amount of drug in solutions.
Apparatus‐2:
It is same as apparatus‐1, except the basket is replaced by a paddle. The dosage form is
allowed to sink to the bottom of the flask before stirring. For dissolution test U.S.P. specifies
the dissolution test medium and volume, type of apparatus to be used, rpm of the shaft, time
limit of the test and assay procedure for. The test tolerance is expressed as a % of the labeled
amount of drug dissolved in the time limit.

Problems in tabletting:
1 Capping
2Lamination/Laminating
3 Chipping
4 Cracking
5 Sticking / Filming
6 Picking
7 Binding
8 Mottling
9 Double impressions
Problems and remedies for tablet coating:
1 Blistering
2 Chipping
3 Cratering
4 Picking
5 Pitting
6 Blooming
7 Blushing
8 Colour variations
9 Infilling
10 Orange peel / Roughness
11 Cracking/Splitting

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CAPSULES
Capsules are solid dosage forms in which the drug or a mixture of drugs is enclosed in Hard
Gelatin Capsule Shells, in soft, soluble shells of gelatin, or in hard or soft shells of any other
suitable material, of various shapes and capacities. They usually contain a single dose of
active ingredient(s) and are intended for oral administration. The consistency of soft shells
may be adjusted by the addition of substances such as Glycerin and Sorbitol. Excipients such
as opaque fillers, antimicrobial preservatives, sweetening agents, flavouring agents and one
or more colouring agents permitted under the Drugs and Cosmetic Rules, 1945 may be added.
Capsules may bear surface markings. The contents of capsules may be of solid, liquid or
paste-like consistency. They consist of the medicament(s) with or without excipients such as
vehicles, solvents, diluents, lubricants, fillers, wetting agents and disintegrating agents. The
contents do not cause deterioration of the shell, but the capsules are attacked by the digestive
fluids thereby releasing the contents. The contents of capsules other than Modified-release
(Sustained-release) Capsules do not contain any added colouring agent.






Capsules

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HARD GELATIN CAPSULES


Hard gelatin capsule filling machine

Hard gelatin capsules contain the medicaments in the solid form. Where two mutually
incompatible drugs are present in the mixture, one of the drugs can be put as a tablet or pellet
or in small capsule and then enclosed with the other drug in a large capsule.
Production Hard gelatin capsules are made by a process that involves dipping shaped pins
into gelatin solutions, after which the gelatin films are dried, trimmed, and removed from the
pins, and the body and cap pieces are joined.

SOFT GELATIN CAPSULES
Soft gelatin capsules made from gelatin (sometimes called soft gels) or other suitable material
require large-scale production methods. The soft gelatin shell is somewhat thicker than that of
hard-shell capsules and may be plasticized by the addition of a polyol such as sorbitol or
glycerin. The ratio of dry plasticizer to dry gelatin determines the “hardness” of the shell and
may be varied to accommodate environmental conditions as well as the nature of the
contents. Like hard shells, the shell composition may include approved dyes and pigments,
opaquing agents such as titanium dioxide, and preservatives. Flavors may be added and up to
5 per cent sucrose may be included for its sweetness and to produce a chewable shell. Soft
gelatin shells normally contain 6 per cent to 13 per cent of water. Soft gelatin capsules shells
are usually formed filled with medicament and sealed in a combined operation on machines.
In some cases, shells for extemporaneous use may be performed. The shells which are thicker
than those of hard capsules are formed to produce capsules which are spherical, oval or
cylindrical with hemispherical ends. Soft gelatin capsules also may be manufactured in a
bubble process that forms seamless spherical capsules. The shells may sometimes contain a
medicament. They may contain a preservative to prevent growth of fungi. The contents of
soft capsules usually consist of liquids or solids dissolved or dispersed in suitable excipients
to give a paste-like consistency. With suitable equipment, powders, granules and other dry

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solids also may be filled into soft-shell capsules. As soft gelatin shells contain appreciable
amounts of water, migration of capsule contents, particularly of water soluble ingredients,
may occur.
Modified-release Capsules:
Modified-release (Sustained release) Capsules are hard or soft capsules in which the contents
or the shell, or both, contain auxiliary substances or are prepared by a special process
designed to modify the rate at which the active ingredients are released.
Enteric Capsules (Gastro-resistant Capsules):
Enteric Capsules are hard or soft capsules prepared in such a manner that the shell resists the
action of the gastric fluid but is attacked by the intestinal fluid to release the contents. During
manufacture, packaging, storage and distribution of capsules, suitable means shall be taken to
ensure their microbial quality; acceptance criteria for microbial quality.

Tests:
Content of active ingredients:
Determine the amount of active ingredients by the method described in the Assay and
calculate the amount of active ingredients in each capsule. The result lies within the range for
the content of act ingredients stated in the monograph. This range is based on the requirement
that 20 capsules, or such other number as may be indicated in the monograph, are used in the
Assay. Where 20 capsules cannot be obtained, a smaller number, which must not be less than
5, may be used, but to allow for sampling errors the tolerances are widened for limits other
than 90 to 110 per cent, proportionately smaller or larger allowances should be made.
Uniformity of weight:
This test is not applicable to capsules that are required to comply with the test for Uniformity
of content for all active ingredients.
Weigh an intact capsule:
Open the capsule without losing any part of the shell and remove the contents as completely
as possible. To remove the contents of a soft capsule the shell may be washed with ether or
other suitable solvent and the shell allowed to stand until the odour of the solvent is no longer
detectable. Weigh the shell. The weight of the contents is the difference between the
weighing. Repeat the procedure with a further 19 capsules. Determine the average weight.
Not more than two of the individual weights deviate from the average weight by more than
the percentage deviation and none deviates by more than twice that percentage.
Uniformity of content:
This test is applicable to capsules that contain less than 10 mg or less than 10 per cent w/w of
active ingredient. For capsules containing more than one active ingredient carry out the test
for each active ingredient that corresponds to the afore-mentioned conditions. The test should
be carried out only after the content of active ingredient(s) in a pooled sample of the capsules
has been shown to be within accepted limits of the stated content.
Disintegration:
The disintegration test is not applicable to Modified-release Capsules. For those Hard
Capsules and Soft Capsules for which the dissolution test is included in the individual
monograph, the test for Disintegration is not required.

27. R.K. Pharmacy College, Azamgarh Page 27


Hard Capsules:


Manual capsule filling machine

Comply with the disintegration test. Unless otherwise directed in the individual monograph
use water as the medium. If the capsules float on the surface of the medium, a disc may be
added. If the capsules adhere to the discs, attach a removable piece of stainless steel woven
gauze with mesh aperture of 2.00 mm to the upper plate of the basket rack assembly and
carry out the test omitting the discs. Operate the apparatus for 30 minutes unless otherwise
directed.
Soft Capsules:
Comply with the disintegration test. Unless otherwise directed in the individual monograph
use water as the medium and add a disc to each tube. Operate the apparatus for 60 minutes
unless otherwise directed.
Enteric Capsules:
Use the apparatus described under disintegration test, using one capsule in each tube. Operate
the apparatus for 2 hours without the discs in 0.1 M hydrochloric acid. No capsule shows
signs of disintegration or of rupture permitting the escape of the contents. Replace the
medium in the vessel with mixed phosphate buffer pH 6.8, add a disc to each tube and
operate the apparatus for a further 60 minutes. Remove the apparatus from the medium and
examine the capsules. They pass the test if no residue remains on the screen or on the

28. R.K. Pharmacy College, Azamgarh Page 28

underside of the discs, or, if a residue remains, it consists of fragments of shell or of a soft
mass with no palpable, unmoistered core.
Pharmaceutical packing:
Definition:
An economical means of providing protection, presentation, identification, information and
convenience for pharmaceuticals product from the moment of production until it is used or
administered.
History of packing material:
Unit Dose Packing:
Unit dose packing was first started in 1927 for a Aspirin based product (ASPRO).
Multi Dose Packing:
Blister packaging was first introduced in American Hospitals.
Visibility in Blister to recognize the product easily
Types of packing materials used by pharmaceutical industry:
Primary Packaging Material:
Also known as Critical Packaging Component
Secondary Packaging Material:
Also known as Non -Critical Packaging Component
Tertiary Packaging Material:
Also known as Non -Critical Packaging Component
Base material / packing materials used by pharmaceutical industry:
Base materials Packing materials
Paper Labels, Leaflets.
Board Catrons ,Display Units
Glass Ampoules, Vials, Syringes, Bottles etc.
Metals
(Aluminium ,Tin Plate)
Collapsible Tubes, Foils etc.
Plastics
(E.g. Polyethylene,
Polypropylene)
Closures, Tubes, PET Bottles etc.

29. R.K. Pharmacy College, Azamgarh Page 29

Metal / Plastic Flip Off Aluminium Seals

Types of packing materials used by pharmaceutical industry:

Alu/Alu Blister Strip Pack Blister Pack


Ceramic Printed Glass Ampoules Amber Glass Vial Glass Ampoule

30. R.K. Pharmacy College, Azamgarh Page 30


One Point Cut Glass Ampoules Color Break Glass Ampoules


Color Labels Tamper Evident Label Product Label

31. R.K. Pharmacy College, Azamgarh Page 31



Product Literature / Leaf Let Bar Code Label

Corrugated Box Plain Aluminium Foil
Importance of packing materials used by pharmaceutical industry:
1. Protection ofProduct
2. Protection from Physical Damage
3. Protection from Chemical Deterioration
4. Protection from Mechanical and Climatic Hazards
5. Protection from Microorganisms
6. Compatibility of Product and Packaging Material
7. Child Resistant
8. Temper Evident
Expectations of pharmaceutical industry from packing industry: Packaging Quality
must be of a good design relevant to the needs of:
1. Product

32. R.K. Pharmacy College, Azamgarh Page 32

2. Manufacturing and Distribution System (of both Customer & Supplier)
Stability Parameters:
1.Protect the Product from Moisture and Gas.
2.Light and Temperature Protection.
3.Microbiological Integrity
4. PH Stability.
Compatibility with Packaging Material:
Migration from the Medicine to the Packaging Components of:
1. Preservatives
2. Volatile actives
Leaching from the packaging to the Medicine of:
1. Stabilizers
2. Plasticizers
3. Anti-oxidant
4. Additives etc
Machine Suitability:
1. Line Speed
2. Tolerances
3. Reliability
Legislation:
1. Fill Weight
2. Labeling
3. Storage
Marketing Aspects:
1. Market Policy
2. Product Code
QUALITY SYSTEMS AND GMP:
1. Strict Safety Norms
2. Quality Certifications like ISO etc
3. Audit from Pharma Industry for GMP conformance
4. Pest Control Programmes
5. Independent Quality Department from Manufacturing Department
6. Written SOP’s and Policies to implement Quality System
7. Controlled Storage Condition
8. Separate Storage Area for RM / Finished Product
9. Good House Keeping / Ware Housing Practices
10. Written Procedure for Line Clearance
11. Fully Equipped Packaging Development Laboratory
12. HEPA filters in the Primary Packaging Material Manufacturing Facility

33. R.K. Pharmacy College, Azamgarh Page 33

13. Availability of Air Curtains &Insecticutors

An ideal Packaging Material Industry,as per GMP and Regulatory requirements should
be equipped with following QC equipments:
1. GSM Measuring Weighing Scale
2. Gauge Meter
3. Viscosity Cup
4. Bond Strength Measuring Unit
5. Bursting Strength Measuring Unit
6. Vacuum Chamber
7. Dart Impact Testing Machine
8. Opacity Meter
9. Pin Hole Checking Table
10. Pantone Shade Card
11. Chemical Analysis Unit
12. VMCH coating machine etc
How the pharma industry can help packing industry?
1.By providing Adequate Training
2.By Regular / Frequent Audits
3.By sharing the Technology




REFERENCE

o Mehta R.M. ‘Pharmaceutics’ 2nd edition Vallabh Prakashan, Page no:-246-252
o Lachman, L., Lieberman, H. A., and Kanig, J. L. (1986 ), The Theory and Practice of
Industrial Pharmacy, 3rd ed. , Philadelphia: Lea & Febiger.
o Allen L. V and Ansel H. C. (2014). Ansel’s Pharmaceutical Dosage Forms and Drug
Delivery Systems. Philadelphia: Lipincott Williams and Wilkins.

34. R.K. Pharmacy College, Azamgarh Page 34

o Dash, A. (2014). Solid Dosage Forms. In A. Dash, S. Singh and J. Tolman (Eds),
Pharmaceutics: Basic Principles and Application to Pharmacy. (pp. 161-180 ). USA:
Elsevier Inc.
o Debjit, B., Duraivel, S., Rajalakshmi, A. and Sampath K. (2014). Tablet
manufacturing process and defects of tablets. Elixir Pharmacy
o Jones D. (2008). Fasttrack Pharmaceutics – Dosage Form and Design. London:
Pharmaceutical Press.
o Sakr, A. A and Alanazi, F. K (2012). Oral Solid Dosage Form. In L.A Felton (Eds.),
Remington Essentials of Pharmaceutics (pp. 581-610). London: Pharmaceutical Press.
o Shayne C. G. (2008), Pharmaceutical Manufacturing Handbook Production and
Processes. New Jersey: John Wiley & Sons, Inc.
o Lachman, L., Lieberman, H. A., and Kanig, J. L. (1986 ), The Theory and Practice of
Industrial Pharmacy, 3rd ed. , Philadelphia: Lea & Febiger Page no:-1-74