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Industrial Training Report
In Partial Fulfillment of Requirement for Award For Degree of
Bachelor of Pharmacy
By
Abhinav Kumar Yadav
Roll no.- 2003150500002
Under the Supervision of
Dr. Anil Kumar Singh
United Institute Of Pharmacy Naini, Prayagraj.
To the
Faculty Of Pharmacy
DR. A.P.J. ABDUL KALAM TECHNICAL UNIVERSITY
DECLARATION
I hereby declared that this report work of “INDUSTRIAL TRAINING” submitted
is there record of an original work done by me under the guidance of Dr. Anil
Kumar Singh, Associate Professor, United Institute Of Pharmacy, Naini,
Prayagraj.
This report work was an empirical finding, and this project work is based on
information collected and carried by me and that to the nest of my knowledge and
belief , it contains no material previously published or written by another person
or material which to a substantial extent has been accepted for the award of any
degree or diploma of the university or other institute of higher learning, except
there due acknowledge has been in the text.
Signature of Student
Abhinav Kumar Yadav
B.Pharm 3rd year
ACKNOWLEDGEMENT
The training opportunity I had with Oxford Pharma, Roorkee Dehradun
Therefore, I consider myself as a very lucky individual as I was provided with an
opportunity to be a part of it. I am also grateful for having a chance to meet so
many wonderful people and professionals who led me though this training period.
I am using this opportunity to express my deepest gratitude and special thanks to
United Institute Of Pharmacy, Naini, Prayagraj, who inspite of being
extraordinarily busy with their duties gave us an opportunity so that we would
learn something so important.
I express my deepest thanks to Prof. (Dr.) Alok Mukerjee (Principal of the
united institute of pharmacy) for taking part in useful decision and giving
necessary advices and guidance and arrange all facilities to make this training
easier. I choose this moment to acknowledge his contribution gratefully.
It is my radiant sentiment to place on record my best regards, deepest sense of
gratitude to Dr. Anil Kumar Singh for their careful and precious guidance with
were extremely valuable for my study both theoretically and practically.
I perceive this opportunity as a big milestone in my career development. I will
strive to use gained skills and knowledge in the best possible way, and I will
continue to work on their improvement.
Thank you.
Sr.no. Contents Page.no.
1. Introduction 1
2. Capsule Manufacturing Defects 4
3. Hard Gelatin Capsule 6
4. Components of Hard Gelatin Capsule 6
5. Capsule Size and Shape 7
6. Raw Material For Hard Gelatin Capsule Shell
Manufacturing
7
7. Manufacturing of Hard Gelatin Capsule 9
8. Manufacturing of Empty Hard Gelatin Capsule 10
9. Filling of Hard Gelatin Capsule 10
10. Soft Gelatin Capsule 13
11. Composition Of Soft Gelatin Capsule 14
12. Vehicles Used in Soft Gelatin Capsule 14
13. Basic Components of Soft Gelatin Capsule 15
14. Manufacture of soft Gelatin Capsule 17
15. Conclusion 19
INDEX
1
CAPSULE
Introduction :
In the manufacture of pharmaceuticals, encapsulation refers to a range of dosage
forms techniques used to enclose medicines in a relatively stable shell known as
a capsule, allowing them to, for example, be taken orally or be used as
suppositories. The two main type of capsules are:
● Hard gelatin capsule, which are typically made using gelatin and contain
dry, powdered ingredients or miniature pellets by e.g. processes of
extrusion or spheronisation. These are made in two halves: a lower
diameter “body” that is filled and then sealed using a higher diameter
“cap”.
● Soft gelatin capsule, primarily used for oils and for active ingredients that
are dissolved or suspended in oil.
Both of these classes of capsule are made from aqueous solutions of gelling
agents, such as animal protein (mainly gelatin) or plant polysaccharides or their
derivatives (such as carrageenans and modified forms of starch and cellulose).
Other ingredients can be added to the gelling agent solution including plasticizers
such as glycerin or sorbitol to decrease the capsule’s hardness, coloring agents,
preservatives, disintegrants, lubricants and surface treatment.
Capsule Manufacturing Process
2
Advantage Of Capsules
1. Ease of use due to fact that it is smooth, slippery and easy to swallow.
2. Suitable for substance having bitter taste and unpleasant odor.
3. As produced in large quantities it is economic, attractive and available in
wide range of colors.
4. Minimum excipients required.
5. Little pressure required to compact the material.
6. Unit dosage form.
7. Easy to store and transport.
Disadvantage Of Capsules
1. Not suitable for highly soluble substances like potassium chloride,
potassium bromide, ammonium chloride, etc.
2. Not suitable for highly efflorescent or deliquescent material.
3. Special conditions are required for storage.
3
4
Capsule Manufacturing Defect
1. Lumpy or mis-shaped capsules :
Sometimes capsules shells form lumps called lumpy or mis-shapen capsule
prevented by maintaining empty shell in temperature range 15°-30°C
relative humidity range 45-55°C avoid exposing to direct sun light or heat.
2. Improper rectification :
In proper rectification capsules are not oriented properly.
3. Failure to separate :
Sometimes cap and body fails to separate due to vacuum generation. Can
be overcome by applying extra vacuum.
4. Dented capsules :
Dents can form on the dome of the cap and /or body this is due to improper
setup of machine or due to overfilling.
5. Telescoping :
This is due to mis-alignment of cap and body, body splits and a portion of
body covers the cap. Rectified by maintaining proper alignment of cap and
body.
6. Popping :
Popping is capsule opening after filling. It is due to overfilling or due to
weak locking machine.
7. Brittleness :
When capsule lose moisture they become brittle (due to poor storage
condition). Filled capsule have hygroscopic substances cause brittleness.
8. Other defects :
● Colour deviation
● Short or long body and cap
● Damaged printing
5
● Dots / specks on capsule
● Holes / scratch
● Bubbles on capsule shell
6
HARD GELATIN CAPSULE
Hard gelatin capsules also known as hard-shell gelatin capsules or two-piece
capsules are solid dosage forms in which one or more medicinal agents and/or
inert materials are enclosed within a small shell. They are a well-established
dosage form that provides solutions to many of today’s drug delivery and
nutraceutical formulation challenges.
A hard gelatin capsule shell consists of two prefabricated, cylindrical sections (a
cap and a body) each of which has one rounded, closed-end and one open end.
The body has a slightly lower diameter than the cap and fits inside the cap.
Hard gelatin capsule shells are fabricated and supplied empty to the
pharmaceutical industry by shell suppliers and are then filled in a separate
operation. During
the capsule filling
unit
operation, the
body is filled
with the drug
substances and the
shell is closed
by bringing the
body and the cap
together.
7
Capsule shells showing features
Components of hard gelatin capsules
Hard gelatin capsule shell is composed largely of gelatin. Other than gelatin, it
may contain materials such as plasticizer, colourants, opacifying agents, and
preservatives which either enable capsule formation or improve their
performance. Hard gelatin capsules also contain 12–16% water, but the water
content can vary, depending on the storage conditions.
Capsule sizes and shapes
Empty hard gelatin capsule shells come in a variety of sizes ranging from an
arbitrary numbering of 000 to 5 with 000 being the largest size and 5 being the
smallest. The shape has remained virtually unchanged since its invention except
for the development of the self-locking capsule during the 1960s when automatic
filling and packaging machines were introduced.
The size of hard gelatin capsule selected for use is determined by requirements
of the formulation, including the dose of the active ingredient and the density and
compaction characteristics of the drug and other components. The first step to
estimating the optimal capsule size for a given product is to determine the density
of the formulation using tapped density for powders and bulk density for pellets,
minitablets, and granules. The appropriate capsule size may then be calculated
using the measured density of the formulation, the target fill weight, and capsule
volume. The fill weight for liquids is calculated by multiplying the specific
gravity of the liquid by the capsule body volume multiplied by 0.9.
8
To accommodate special needs, some intermediate sizes (‘elongated sizes’) are
produced. These capsule sizes typically have an extra 10% of fill volume
compared to the standard sizes e.g. elongated size 00 capsules (00el), elongated
size 0 capsules (0el), elongated size 1 capsules (1el), elongated size 2 capsules
(2el) etc. The table below shows capsule volumes and typical fill weights for
formulations with different tapped densities.
Capsule volumes and typical fill weights for formulations with different tapped densities
Raw materials for hard gelatin capsule shell
manufacturing
Hard gelatin capsule shell is composed largely of gelatin. Other than gelatin, it
may contain materials such as plasticizer, colourants, opacifying agents, and
preservatives which either enable capsule formation or improve their
performance. Hard gelatin capsules also contain 12–16% water, but the water
content can vary, depending on the storage conditions.
A. Gelatin
Gelatin is by far the most common and most well-known material used to produce
hard capsule shells. It is a generic term for a mixture of purified protein fractions
obtained from irreversible hydrolytic extraction of collagen obtained from the
skin, white connective tissue, and bones of animals.
Depending on the source of the collagen and the method of extraction, two types
of gelatin can be produced – type A gelatin and type B gelatin. Type A gelatin is
made from pork skin via acid hydrolysis and has an isoelectric point between 7.0
and 9.0. Type B gelatin is prepared by alkaline hydrolysis of bovine bones and
has an isoelectric point between 4.8 and 5.0. Because of this difference in
isoelectric points, both gelatins show solubility differences at different pH values.
Traditionally capsules may be manufactured by using both types of gelatin, but
combinations of pork skin and bone gelatin are often used to optimize shell
characteristics because bone gelatin contributes firmness, whereas pork skin
gelatin contributes plasticity and clarity.
9
Gelatin derived from Gelatin grade is further specified by bloom strength. This is
measured in a Bloom gelometer which determines the weight in grams that is
required to depress a standard plunger in a 6.67% w/w gel under standard
conditions.
Gelatin is stable in air when dry but is subject to microbial decomposition when
it becomes moist.
B. Plasticizer
Plasticizers are added to gelatin to reduce the rigidity of the polymer and make it
more pliable. Common examples of plasticizers are glycerine and polyhydric
alcohol. Water is also a good plasticizer and is naturally present in the gelatin.
C. Colourants
Most frequently, hard gelatin capsules are coloured to enhance the aesthetic
properties and also to act as a means of identifying the product. Colorants used
must meet the regulatory requirements of those countries where the product will
be sold. Examples of commonly used capsule colourants include synthetic dyes
such as azo dyes and xanthene dyes. Iron oxide pigments are also used.
D. Opacifying agents
Opacifiers (e.g., titanium dioxide) may be included to make clear gelatin opaque.
Opaque capsules may be employed to provide protection against light or to
conceal the contents.
E. Preservatives
Preservatives (often parabens esters) were formerly added to hard capsules as an
in-process aid in order to prevent microbiological contamination during
manufacture. Manufacturers operating their plants to Good Manufacturing
Practice (GMP) guidelines no longer use them. In the finished capsules, the
moisture levels, 12–16% w/ v, are such that the water activity will not support
bacterial growth because the moisture is too strongly bound to the gelatin
molecule.
Manufacture of Hard Gelatin Capsules
10
The sequence of two-piece hard gelatin capsule shell manufacture
Manufacture of empty hard gelatin capsules
Hard gelatin capsules are manufactured using a dip-coating method and the
various stages involved are as follows:
Step 1: Preparation of the gelatin solution (dipping solution)
Step 2: Dip-coating the gelatin solution on to metal pins (moulds)
Step 3: Rotation of the Dip-coated pins
Step 4: Drying of the gelatin-coated pins
Step 5: Stripping and trimming
Step 6: Joining of the trimmed capsule shell
Step 7: Printing
Filling of hard gelatin capsules:
11
The filling of hard gelatin capsules is an established technology, with equipment
available ranging from that for very small-scale manual filling (e.g., Feton
capsule filling machine), through intermediate-scale semi-automatic filling to
large-scale fully automatic filling. Hard gelatin capsules can also be hand-filled
one at a time, as done in a compounding pharmacy. The difference between the
many methods available is the way in which the dose of material is measured into
the capsule body.
The basic steps in filling hard gelatin capsules include:
1. Rectification of capsules (placing empty gelatin capsules on the removable
plate with bodies facing downward).
2. Separation of caps from bodies.
3. Dosing of fill material (The body is filled with the formulation manually
using a plastic spatula, and the excess powder is removed).
4. Replacement of caps/ closing capsule shells and
5. Ejection of filled capsules
Filling of powder formulations into hard gelatin
capsules
Hard gelatin capsules can be filled by hand for research or experimental purposes
or when filling a small number of capsules in the pharmacy. This is done by
placing the powder to be filled on a sheet of clean paper or on a pill tile or
porcelain plate and pressing the open end of the capsule downward until it is
filled. The cap is then placed to close the capsule.
On a small-scale manufacture, hard gelatin capsules can be filled manually using
a manual or a hand-operated capsule machine. This is done by directly filling the
powder into the capsule shell and relying on the bulk/tapped density of the
powder to get the correct dose for the volume of the capsule shell used. The
various types of hand-operated capsule machines have capacities ranging from
24 to 300 capsules and, when efficiently operated, are capable of producing about
200 to 2,000 capsules per hour.
Large scale production involves the use of machines that come in great variety of
shapes and sizes, varying from semi- to fully automatic and ranging in output
from 3000 to 150 000 per hour. Powder filling is accomplished by either of the
two dosing devices: dosator device or dosing disk/tamping device.
The dosator device uses an empty tube that dips into powder bed, which is
maintained at a height approximately two-fold greater than the desired length of
12
the plug. The dosator piston’s forward movement helps form the plug, which is
then transferred to the body of the capsule, and released.
Dosator filling principles
Filling of liquids/semisolid formulations into hard
gelatin capsules
As drug discovery continues to yield poorly water-soluble molecules, there is an
increasing need for formulation techniques that can improve drug solubility.
One such approach is the use of liquid-based formulations containing lipids,
solvents, or surfactants, usually in combination, to improve drug solubility and
bioavailability. The final formulation may be filled through piston pump
systems into hard gelatin capsules as a room temperature liquid, or as a molten
semisolid.
The filling of a liquid or semi-solid formulation is dependent on the viscoelastic
properties of the formulation and the need to fulfil certain characteristics at the
filling temperature. As a general rule, the formulation should have a viscosity of
between 50 and 1000 Centipoise (cP) (although formulations of much higher
viscosity can be suitable for manufacturing) and should not exceed 70 °C.
The particle size in suspension should ideally be less than 20 µm and formulations
should be such that no stringing, dripping, splashes or solidification of the
formulation should occur at the dosing nozzle. Unless a hot-melt is filled that
completely solidifies below 40 °C, hard capsules are recommended to be band or
fusion sealed using separate band sealing or Liquid Encapsulation Microspray
Sealing (LEMS®) sealing equipment. For research purposes, a machine that is
capable of filling and sealing 1500 capsules an hour (e.g. CFS® 1500) has been
developed.
13
Note: If hard gelatin capsules cannot be used because of any formulation,
preference, or cultural reason, alternative materials such as polymer-based shells
or hypromellose may be used.
Examples of hard gelatin capsules :
Examples of solid-filled hard gelatin capsules
● Cinobac – Cinoxacin (Eli Lilly and Co.)
● Amphetamine and dextroamphetamine – Adderal XL (Shire
Pharmaceuticals)
● Methylphenidate hydrochloride – Ritalin LA (Novartis)
● Didanosine – Videx EC (Bristol Myers)
Examples of liquid- or semi-solid-filled hard gelatin
capsules
● Vancomycin – Vancodin (Lilly)
● Captopril – Captopril-R (Sankyo)
● Ibuprofen – Solufen (SMB Ivax)
● Piroxicam – Solicam (SMB)
SOFT GELATIN CAPSULE
Soft gelatin capsules, also known as softgels or soft elastic capsules, are
hermetically sealed one-piece capsules containing a liquid or a semisolid fill
without a bubble of air or gas. They are made from a more flexible, gelatin film
plasticized by the addition of glycerine, sorbitol, or a similar polyol.
As with hard gelatin capsules, soft gelatin capsules are predominantly
administered orally. Some can be formulated and manufactured to produce a
number of different drug delivery systems such as
a. Chewable softgels where a highly-flavoured shell is chewed to release the
drug liquid fill matrix
b. Suckable softgels which consist of a gelatin shell containing the flavoured
medicament to be sucked and a liquid matrix (or just air inside the capsule)
14
c. Twist-off softgels which are designed with a tag to be twisted or snipped
off, thereby allowing access to the fill material and
d. Meltable softgels designed for use as pessaries or suppositories.
Schematic diagrams illustrating different shapes of soft gelatin capsules
Soft gelatin capsules have grown in popularity in recent years because they
enable administration of liquids in a solid dosage form with a bioavailability
advantage over other commonly used solid dosage forms (e.g., tablets). They
are available in a variety of sizes, shapes, and colours that may be specific to the
manufacturer.
Composition of soft gelatin capsule shell
The major components of soft gelatin capsule shell are gelatin, plasticizer and
water. Besides these three components, soft gelatin capsule shell may contain
other ingredients such as colourants and/ or opacifiers for visual appeal and/or
reducing the penetration of light for the encapsulation of photosensitive drug
substances.
Flavours and sweeteners may be added to improve palatability. Preservatives e.g.,
potassium sorbate, and methyl, ethyl, and propyl hydroxybenzoate are added to
prevent the growth of bacteria and mould in the gelatin solution during storage.
Acid-resistant polymers when present in the capsule shell formulation are used to
impart enteric release characteristics. They can also be used to formulate
chewable soft gelatin capsules e.g., ChildLife’s Pure DHA chewable 250 mg
softgel capsule.
Component Function Typical content (% w/w)
Gelatin Polymeric base 66.3
Glycerine Plasticizer 33.0
15
Methylparaben + propylparaben (80/20 ratio) Preservative 0.1
Colour Colourant 0.1
Titanium dioxide Opacifier 0.5
Water Solvent/process aid q.s. (0.7–1.3 × of gelatin)
Typical composition of a soft gelatin capsule shell
Types of vehicles used in soft gelatin capsules :
Softgels are prepared to contain a variety of liquid, paste, and dry fills. Liquids
that may be encapsulated into soft gelatin capsules include the following:
1. Water-immiscible volatile and non-volatile liquids such as vegetable and
aromatic oils, aromatic and aliphatic hydrocarbons, chlorinated
hydrocarbons, ethers, esters, alcohols, and organic acids.
2. Water-miscible non-volatile liquids, such as polyethylene glycols, and
nonionic surface-active agents, such as polysorbate 80.
3. Water-miscible and relatively non-volatile compounds such as propylene
glycol and isopropyl alcohol, depending on factors such as concentration
used and packaging conditions
Note: Liquids that can easily migrate through the capsule shell are not suitable
for soft gelatin capsules. These materials include water above 5% and low
molecular weight water-soluble and volatile organic compounds such as alcohols,
ketones, acids, amines, and esters.
Basic components of soft gelatin capsule shell
The various components of the soft gelatin capsule shell are as follows:
A. Gelatin
Similar to hard gelatin capsule shells, the basic component of soft gelatin capsule
shell is gelatin. A large number of different gelatin shell formulations are
available depending on the nature of the liquid fill matrix. Most commonly, the
gelatin is alkali- (or base-) processed (type B) gelatin and it normally constitutes
40% of the wet molten gel mass. Type A acid-processed gelatin can also be used.
The properties of gelatin shells are controlled by the choice of gelatin grade and
by adjusting the concentration of plasticizer in the shell. The physicochemical
properties of gelatin are controlled to allow
1. Adequate flow at desired temperatures to form ribbons of defined
thickness, texture, mechanical strength, and elasticity.
16
2. Ribbons to be easily removed from the drums, stretch during filling, seal
the temperature below the melting point of the film, and dry quickly under
ambient conditions to an adequate and a reproducible strength.
Physicochemical properties of gelatin important to capsule formation include gel
strength, viscosity, change in viscosity with temperature and shear, melting point,
settling point (temperature), settling time, particle size (affects time to dissolve),
and molecular weight distribution (affects viscosity and strength).
B. Plasticising agents
Plasticizing agents are added in a soft gelatin capsule formulation to ensure
adequate flexibility. They interact with gelatin chains to reduce the glass
transition temperature (Tg) of the gelatin shell and/or promotes the retention of
moisture (hygroscopicity). The most common plasticizer used for soft gelatin
capsules is glycerol. Sorbitol, maltitol, and polypropylene glycol can also be used
in combination with glycerol.
Glycerol derives its plasticizing ability primarily from its direct interactions with
gelatin. In contrast, sorbitol is an indirect plasticizer because it primarily acts as
a moisture retentive agent. Compared to hard gelatin capsules and tablet film
coatings, a relatively large amount (20 -30% w/w) of plasticizers are added in a
soft gelatin capsule formulation to ensure adequate flexibility. The amount and
choice of the plasticizer contribute to the hardness of the final product and may
even affect its dissolution or disintegration characteristics, as well as its physical
and chemical stability.
C. Water
Water usually accounts for 30-40 % of the wet gel formulation and its presence
is important both during the manufacturing process (to facilitate manufacture)
and in the finished product to ensure that the capsule is flexible. The desirable
water content of the gelatin solution used to produce a soft gelatin capsule shell
depends on the viscosity of the specific grade of gelatin used. It usually ranges
between 0.7 and 1.3 parts of water to each part of dry gelatin.
After the capsule is formed, most of the water is removed from the soft gelatin
capsules through controlled drying. The finished soft gelatin capsules contain 13–
16 % w/w water, which represents the proportion of water that is bound to the
gelatin in the soft gel shell. This level of water is important for good physical
stability, because in harsh storage conditions softgels will become either too soft
and fuse together, or too hard and embrittled.
17
D. Preservative
Preservatives are often added to prevent the growth of bacteria and mould in the
gelatin solution during storage. Examples of commonly used as preservatives
include potassium sorbate, and methyl, ethyl, and propyl hydroxybenzoate.
E. Colorant and/or opacifier
A colourant (soluble dyes, or insoluble pigments or lakes) and/or opacifier (e.g.,
titanium dioxide) may be added to the shell for visual appeal and/or reducing the
penetration of light for the encapsulation of a photosensitive drug. The colour of
the capsule shell is generally chosen to be darker than that of its contents.
F. Other excipients
Other, infrequently, used excipients can include flavouring agents and sweeteners
to improve palatability. Acid-resistant polymers are used to impart enteric release
characteristics. They can also be used to formulate chewable soft gelatin capsules.
A chelating agent, such as ethylene diamine tetracetic acid (EDTA), can be added
to prevent chemical degradation of oxidation sensitive drugs catalysed by free
metals in gelatin, such as iron.
Manufacture of Soft Gelatin Capsules
Softgels are manufactured using the following methods
1. Plate process
2. Rotary die process
3. Reciprocating die process
4. Accogel process
5. Seamless process
Plate process
This is the oldest commercial process used in the manufacture of soft gelatin
capsules. In this process, a warmed sheet of plain or coloured plasticized gelatin
is placed over a die plate having a number of depression or moulds or numerous
die pockets. By applying vacuum, the sheet is drawn into these depressions or
pockets to form capsule wells. The capsule wells are then filled with medication-
containing liquid. A second sheet of gelatin is carefully placed on top of the filled
wells followed by the top plate of the mould. Pressure is then applied to the
combined plate to form, seal and cut the capsules into individual units. This
method is used for small scale preparation of soft gelatin capsules and capsules
formed generally, had one flat side.
18
The major problems with this method of manufacturing softgels were the lack of
dosage uniformity, high manufacturing losses, and its labour-/cost-intensiveness.
This equipment is no longer available.
Rotary Die Process
Most soft gelatin capsules are prepared by the rotary die process, a method
developed and perfected in 1933 by Robert P. Scherer. This process almost
eliminated all the problems associated with the plate process and produced soft
gelatin capsules with improved uniformity and high standards of accuracy.
In this process, two plasticized gelatin ribbons (prepared in the rotary-die
machine) are continuously and simultaneously fed with the liquid, semiliquid or
paste fill between the rollers of the rotary die mechanism. The forced injection of
the feed material between the two ribbons causes the gelatin to swell into the left-
and right-hand die pockets which govern the size and shape of the softgels as they
converge. As the die rolls rotate, the convergence of the matching dies pockets
hermetically seals and cuts out the filled capsules.
Softgel formation
mechanism (rotary die mechanism)
The precise and extremely low clearance of the rotating parts demands continuous
lubrication of the machine to avoid even a slight build-up. The lubrication oil
should, therefore, be a GRAS (generally recognized as safe) material.
Immediately after manufacture, the formed capsules automatically undergo
volatile solvent washing to remove any traces of lubricating oil from the exterior
of the capsules. The capsules are then conveyed to a drying station and dried on
trays, either in air or under vacuum, to equilibrium moisture content to about 6 –
10 % with forced conditioned air of 20% – 30% relative humidity at 21°C–24°C.
The drying technique may proceed with an infrared drying step to speed up the
process.
After drying is complete, capsules are then be transferred to the inspection station
and sampled for release, after performing the required quality control tests for
19
sizes sorting, colour sorting, and packaging. Depending on the manufacturer,
additional finishing operations such as off-line print can be performed.
CONCLUSION
Thus at the end I have reach at conclusion that during my one month training in
Oxford Pharma, Roorkee Dehradun I have understand the environment of
industry and how much company’s staff do the hard work in the production of
such a bulk number of product and how one can cope with the problem while
working. A pharmaceutical manufacturing unit is placed where not only been best
possible formulation are prepared to serve the social surrounding but also
industrial training program carried out to prepare technically skilled
manufacturing chemist and analysts.
In this industry both the above two functions are carried out under the supervision
of well skilled experienced and technical persons with complete attention and
honesty that improves not only the growth profile of industry but also produce
best chemist and analysts in future.
I wish for a sharp growth profile of the industry in the coming days and I also
admire it to be one of the best places for producing better chemists and analysts
beyond the formulation.
My opinion about industry is best places are occasionally been noted by someone
this is one of them noted by me.
I like the environment, staffs and head of departments and heartily wish to work
with them ever when an opportunity is given to me.
20

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Industrial training report 2 United institute of pharmacy

  • 1. Industrial Training Report In Partial Fulfillment of Requirement for Award For Degree of Bachelor of Pharmacy By Abhinav Kumar Yadav Roll no.- 2003150500002 Under the Supervision of Dr. Anil Kumar Singh United Institute Of Pharmacy Naini, Prayagraj. To the Faculty Of Pharmacy DR. A.P.J. ABDUL KALAM TECHNICAL UNIVERSITY
  • 2. DECLARATION I hereby declared that this report work of “INDUSTRIAL TRAINING” submitted is there record of an original work done by me under the guidance of Dr. Anil Kumar Singh, Associate Professor, United Institute Of Pharmacy, Naini, Prayagraj. This report work was an empirical finding, and this project work is based on information collected and carried by me and that to the nest of my knowledge and belief , it contains no material previously published or written by another person or material which to a substantial extent has been accepted for the award of any degree or diploma of the university or other institute of higher learning, except there due acknowledge has been in the text. Signature of Student Abhinav Kumar Yadav B.Pharm 3rd year
  • 3. ACKNOWLEDGEMENT The training opportunity I had with Oxford Pharma, Roorkee Dehradun Therefore, I consider myself as a very lucky individual as I was provided with an opportunity to be a part of it. I am also grateful for having a chance to meet so many wonderful people and professionals who led me though this training period. I am using this opportunity to express my deepest gratitude and special thanks to United Institute Of Pharmacy, Naini, Prayagraj, who inspite of being extraordinarily busy with their duties gave us an opportunity so that we would learn something so important. I express my deepest thanks to Prof. (Dr.) Alok Mukerjee (Principal of the united institute of pharmacy) for taking part in useful decision and giving necessary advices and guidance and arrange all facilities to make this training easier. I choose this moment to acknowledge his contribution gratefully. It is my radiant sentiment to place on record my best regards, deepest sense of gratitude to Dr. Anil Kumar Singh for their careful and precious guidance with were extremely valuable for my study both theoretically and practically. I perceive this opportunity as a big milestone in my career development. I will strive to use gained skills and knowledge in the best possible way, and I will continue to work on their improvement. Thank you.
  • 4. Sr.no. Contents Page.no. 1. Introduction 1 2. Capsule Manufacturing Defects 4 3. Hard Gelatin Capsule 6 4. Components of Hard Gelatin Capsule 6 5. Capsule Size and Shape 7 6. Raw Material For Hard Gelatin Capsule Shell Manufacturing 7 7. Manufacturing of Hard Gelatin Capsule 9 8. Manufacturing of Empty Hard Gelatin Capsule 10 9. Filling of Hard Gelatin Capsule 10 10. Soft Gelatin Capsule 13 11. Composition Of Soft Gelatin Capsule 14 12. Vehicles Used in Soft Gelatin Capsule 14 13. Basic Components of Soft Gelatin Capsule 15 14. Manufacture of soft Gelatin Capsule 17 15. Conclusion 19 INDEX
  • 5. 1 CAPSULE Introduction : In the manufacture of pharmaceuticals, encapsulation refers to a range of dosage forms techniques used to enclose medicines in a relatively stable shell known as a capsule, allowing them to, for example, be taken orally or be used as suppositories. The two main type of capsules are: ● Hard gelatin capsule, which are typically made using gelatin and contain dry, powdered ingredients or miniature pellets by e.g. processes of extrusion or spheronisation. These are made in two halves: a lower diameter “body” that is filled and then sealed using a higher diameter “cap”. ● Soft gelatin capsule, primarily used for oils and for active ingredients that are dissolved or suspended in oil. Both of these classes of capsule are made from aqueous solutions of gelling agents, such as animal protein (mainly gelatin) or plant polysaccharides or their derivatives (such as carrageenans and modified forms of starch and cellulose). Other ingredients can be added to the gelling agent solution including plasticizers such as glycerin or sorbitol to decrease the capsule’s hardness, coloring agents, preservatives, disintegrants, lubricants and surface treatment. Capsule Manufacturing Process
  • 6. 2 Advantage Of Capsules 1. Ease of use due to fact that it is smooth, slippery and easy to swallow. 2. Suitable for substance having bitter taste and unpleasant odor. 3. As produced in large quantities it is economic, attractive and available in wide range of colors. 4. Minimum excipients required. 5. Little pressure required to compact the material. 6. Unit dosage form. 7. Easy to store and transport. Disadvantage Of Capsules 1. Not suitable for highly soluble substances like potassium chloride, potassium bromide, ammonium chloride, etc. 2. Not suitable for highly efflorescent or deliquescent material. 3. Special conditions are required for storage.
  • 7. 3
  • 8. 4 Capsule Manufacturing Defect 1. Lumpy or mis-shaped capsules : Sometimes capsules shells form lumps called lumpy or mis-shapen capsule prevented by maintaining empty shell in temperature range 15°-30°C relative humidity range 45-55°C avoid exposing to direct sun light or heat. 2. Improper rectification : In proper rectification capsules are not oriented properly. 3. Failure to separate : Sometimes cap and body fails to separate due to vacuum generation. Can be overcome by applying extra vacuum. 4. Dented capsules : Dents can form on the dome of the cap and /or body this is due to improper setup of machine or due to overfilling. 5. Telescoping : This is due to mis-alignment of cap and body, body splits and a portion of body covers the cap. Rectified by maintaining proper alignment of cap and body. 6. Popping : Popping is capsule opening after filling. It is due to overfilling or due to weak locking machine. 7. Brittleness : When capsule lose moisture they become brittle (due to poor storage condition). Filled capsule have hygroscopic substances cause brittleness. 8. Other defects : ● Colour deviation ● Short or long body and cap ● Damaged printing
  • 9. 5 ● Dots / specks on capsule ● Holes / scratch ● Bubbles on capsule shell
  • 10. 6 HARD GELATIN CAPSULE Hard gelatin capsules also known as hard-shell gelatin capsules or two-piece capsules are solid dosage forms in which one or more medicinal agents and/or inert materials are enclosed within a small shell. They are a well-established dosage form that provides solutions to many of today’s drug delivery and nutraceutical formulation challenges. A hard gelatin capsule shell consists of two prefabricated, cylindrical sections (a cap and a body) each of which has one rounded, closed-end and one open end. The body has a slightly lower diameter than the cap and fits inside the cap. Hard gelatin capsule shells are fabricated and supplied empty to the pharmaceutical industry by shell suppliers and are then filled in a separate operation. During the capsule filling unit operation, the body is filled with the drug substances and the shell is closed by bringing the body and the cap together.
  • 11. 7 Capsule shells showing features Components of hard gelatin capsules Hard gelatin capsule shell is composed largely of gelatin. Other than gelatin, it may contain materials such as plasticizer, colourants, opacifying agents, and preservatives which either enable capsule formation or improve their performance. Hard gelatin capsules also contain 12–16% water, but the water content can vary, depending on the storage conditions. Capsule sizes and shapes Empty hard gelatin capsule shells come in a variety of sizes ranging from an arbitrary numbering of 000 to 5 with 000 being the largest size and 5 being the smallest. The shape has remained virtually unchanged since its invention except for the development of the self-locking capsule during the 1960s when automatic filling and packaging machines were introduced. The size of hard gelatin capsule selected for use is determined by requirements of the formulation, including the dose of the active ingredient and the density and compaction characteristics of the drug and other components. The first step to estimating the optimal capsule size for a given product is to determine the density of the formulation using tapped density for powders and bulk density for pellets, minitablets, and granules. The appropriate capsule size may then be calculated using the measured density of the formulation, the target fill weight, and capsule volume. The fill weight for liquids is calculated by multiplying the specific gravity of the liquid by the capsule body volume multiplied by 0.9.
  • 12. 8 To accommodate special needs, some intermediate sizes (‘elongated sizes’) are produced. These capsule sizes typically have an extra 10% of fill volume compared to the standard sizes e.g. elongated size 00 capsules (00el), elongated size 0 capsules (0el), elongated size 1 capsules (1el), elongated size 2 capsules (2el) etc. The table below shows capsule volumes and typical fill weights for formulations with different tapped densities. Capsule volumes and typical fill weights for formulations with different tapped densities Raw materials for hard gelatin capsule shell manufacturing Hard gelatin capsule shell is composed largely of gelatin. Other than gelatin, it may contain materials such as plasticizer, colourants, opacifying agents, and preservatives which either enable capsule formation or improve their performance. Hard gelatin capsules also contain 12–16% water, but the water content can vary, depending on the storage conditions. A. Gelatin Gelatin is by far the most common and most well-known material used to produce hard capsule shells. It is a generic term for a mixture of purified protein fractions obtained from irreversible hydrolytic extraction of collagen obtained from the skin, white connective tissue, and bones of animals. Depending on the source of the collagen and the method of extraction, two types of gelatin can be produced – type A gelatin and type B gelatin. Type A gelatin is made from pork skin via acid hydrolysis and has an isoelectric point between 7.0 and 9.0. Type B gelatin is prepared by alkaline hydrolysis of bovine bones and has an isoelectric point between 4.8 and 5.0. Because of this difference in isoelectric points, both gelatins show solubility differences at different pH values. Traditionally capsules may be manufactured by using both types of gelatin, but combinations of pork skin and bone gelatin are often used to optimize shell characteristics because bone gelatin contributes firmness, whereas pork skin gelatin contributes plasticity and clarity.
  • 13. 9 Gelatin derived from Gelatin grade is further specified by bloom strength. This is measured in a Bloom gelometer which determines the weight in grams that is required to depress a standard plunger in a 6.67% w/w gel under standard conditions. Gelatin is stable in air when dry but is subject to microbial decomposition when it becomes moist. B. Plasticizer Plasticizers are added to gelatin to reduce the rigidity of the polymer and make it more pliable. Common examples of plasticizers are glycerine and polyhydric alcohol. Water is also a good plasticizer and is naturally present in the gelatin. C. Colourants Most frequently, hard gelatin capsules are coloured to enhance the aesthetic properties and also to act as a means of identifying the product. Colorants used must meet the regulatory requirements of those countries where the product will be sold. Examples of commonly used capsule colourants include synthetic dyes such as azo dyes and xanthene dyes. Iron oxide pigments are also used. D. Opacifying agents Opacifiers (e.g., titanium dioxide) may be included to make clear gelatin opaque. Opaque capsules may be employed to provide protection against light or to conceal the contents. E. Preservatives Preservatives (often parabens esters) were formerly added to hard capsules as an in-process aid in order to prevent microbiological contamination during manufacture. Manufacturers operating their plants to Good Manufacturing Practice (GMP) guidelines no longer use them. In the finished capsules, the moisture levels, 12–16% w/ v, are such that the water activity will not support bacterial growth because the moisture is too strongly bound to the gelatin molecule. Manufacture of Hard Gelatin Capsules
  • 14. 10 The sequence of two-piece hard gelatin capsule shell manufacture Manufacture of empty hard gelatin capsules Hard gelatin capsules are manufactured using a dip-coating method and the various stages involved are as follows: Step 1: Preparation of the gelatin solution (dipping solution) Step 2: Dip-coating the gelatin solution on to metal pins (moulds) Step 3: Rotation of the Dip-coated pins Step 4: Drying of the gelatin-coated pins Step 5: Stripping and trimming Step 6: Joining of the trimmed capsule shell Step 7: Printing Filling of hard gelatin capsules:
  • 15. 11 The filling of hard gelatin capsules is an established technology, with equipment available ranging from that for very small-scale manual filling (e.g., Feton capsule filling machine), through intermediate-scale semi-automatic filling to large-scale fully automatic filling. Hard gelatin capsules can also be hand-filled one at a time, as done in a compounding pharmacy. The difference between the many methods available is the way in which the dose of material is measured into the capsule body. The basic steps in filling hard gelatin capsules include: 1. Rectification of capsules (placing empty gelatin capsules on the removable plate with bodies facing downward). 2. Separation of caps from bodies. 3. Dosing of fill material (The body is filled with the formulation manually using a plastic spatula, and the excess powder is removed). 4. Replacement of caps/ closing capsule shells and 5. Ejection of filled capsules Filling of powder formulations into hard gelatin capsules Hard gelatin capsules can be filled by hand for research or experimental purposes or when filling a small number of capsules in the pharmacy. This is done by placing the powder to be filled on a sheet of clean paper or on a pill tile or porcelain plate and pressing the open end of the capsule downward until it is filled. The cap is then placed to close the capsule. On a small-scale manufacture, hard gelatin capsules can be filled manually using a manual or a hand-operated capsule machine. This is done by directly filling the powder into the capsule shell and relying on the bulk/tapped density of the powder to get the correct dose for the volume of the capsule shell used. The various types of hand-operated capsule machines have capacities ranging from 24 to 300 capsules and, when efficiently operated, are capable of producing about 200 to 2,000 capsules per hour. Large scale production involves the use of machines that come in great variety of shapes and sizes, varying from semi- to fully automatic and ranging in output from 3000 to 150 000 per hour. Powder filling is accomplished by either of the two dosing devices: dosator device or dosing disk/tamping device. The dosator device uses an empty tube that dips into powder bed, which is maintained at a height approximately two-fold greater than the desired length of
  • 16. 12 the plug. The dosator piston’s forward movement helps form the plug, which is then transferred to the body of the capsule, and released. Dosator filling principles Filling of liquids/semisolid formulations into hard gelatin capsules As drug discovery continues to yield poorly water-soluble molecules, there is an increasing need for formulation techniques that can improve drug solubility. One such approach is the use of liquid-based formulations containing lipids, solvents, or surfactants, usually in combination, to improve drug solubility and bioavailability. The final formulation may be filled through piston pump systems into hard gelatin capsules as a room temperature liquid, or as a molten semisolid. The filling of a liquid or semi-solid formulation is dependent on the viscoelastic properties of the formulation and the need to fulfil certain characteristics at the filling temperature. As a general rule, the formulation should have a viscosity of between 50 and 1000 Centipoise (cP) (although formulations of much higher viscosity can be suitable for manufacturing) and should not exceed 70 °C. The particle size in suspension should ideally be less than 20 µm and formulations should be such that no stringing, dripping, splashes or solidification of the formulation should occur at the dosing nozzle. Unless a hot-melt is filled that completely solidifies below 40 °C, hard capsules are recommended to be band or fusion sealed using separate band sealing or Liquid Encapsulation Microspray Sealing (LEMS®) sealing equipment. For research purposes, a machine that is capable of filling and sealing 1500 capsules an hour (e.g. CFS® 1500) has been developed.
  • 17. 13 Note: If hard gelatin capsules cannot be used because of any formulation, preference, or cultural reason, alternative materials such as polymer-based shells or hypromellose may be used. Examples of hard gelatin capsules : Examples of solid-filled hard gelatin capsules ● Cinobac – Cinoxacin (Eli Lilly and Co.) ● Amphetamine and dextroamphetamine – Adderal XL (Shire Pharmaceuticals) ● Methylphenidate hydrochloride – Ritalin LA (Novartis) ● Didanosine – Videx EC (Bristol Myers) Examples of liquid- or semi-solid-filled hard gelatin capsules ● Vancomycin – Vancodin (Lilly) ● Captopril – Captopril-R (Sankyo) ● Ibuprofen – Solufen (SMB Ivax) ● Piroxicam – Solicam (SMB) SOFT GELATIN CAPSULE Soft gelatin capsules, also known as softgels or soft elastic capsules, are hermetically sealed one-piece capsules containing a liquid or a semisolid fill without a bubble of air or gas. They are made from a more flexible, gelatin film plasticized by the addition of glycerine, sorbitol, or a similar polyol. As with hard gelatin capsules, soft gelatin capsules are predominantly administered orally. Some can be formulated and manufactured to produce a number of different drug delivery systems such as a. Chewable softgels where a highly-flavoured shell is chewed to release the drug liquid fill matrix b. Suckable softgels which consist of a gelatin shell containing the flavoured medicament to be sucked and a liquid matrix (or just air inside the capsule)
  • 18. 14 c. Twist-off softgels which are designed with a tag to be twisted or snipped off, thereby allowing access to the fill material and d. Meltable softgels designed for use as pessaries or suppositories. Schematic diagrams illustrating different shapes of soft gelatin capsules Soft gelatin capsules have grown in popularity in recent years because they enable administration of liquids in a solid dosage form with a bioavailability advantage over other commonly used solid dosage forms (e.g., tablets). They are available in a variety of sizes, shapes, and colours that may be specific to the manufacturer. Composition of soft gelatin capsule shell The major components of soft gelatin capsule shell are gelatin, plasticizer and water. Besides these three components, soft gelatin capsule shell may contain other ingredients such as colourants and/ or opacifiers for visual appeal and/or reducing the penetration of light for the encapsulation of photosensitive drug substances. Flavours and sweeteners may be added to improve palatability. Preservatives e.g., potassium sorbate, and methyl, ethyl, and propyl hydroxybenzoate are added to prevent the growth of bacteria and mould in the gelatin solution during storage. Acid-resistant polymers when present in the capsule shell formulation are used to impart enteric release characteristics. They can also be used to formulate chewable soft gelatin capsules e.g., ChildLife’s Pure DHA chewable 250 mg softgel capsule. Component Function Typical content (% w/w) Gelatin Polymeric base 66.3 Glycerine Plasticizer 33.0
  • 19. 15 Methylparaben + propylparaben (80/20 ratio) Preservative 0.1 Colour Colourant 0.1 Titanium dioxide Opacifier 0.5 Water Solvent/process aid q.s. (0.7–1.3 × of gelatin) Typical composition of a soft gelatin capsule shell Types of vehicles used in soft gelatin capsules : Softgels are prepared to contain a variety of liquid, paste, and dry fills. Liquids that may be encapsulated into soft gelatin capsules include the following: 1. Water-immiscible volatile and non-volatile liquids such as vegetable and aromatic oils, aromatic and aliphatic hydrocarbons, chlorinated hydrocarbons, ethers, esters, alcohols, and organic acids. 2. Water-miscible non-volatile liquids, such as polyethylene glycols, and nonionic surface-active agents, such as polysorbate 80. 3. Water-miscible and relatively non-volatile compounds such as propylene glycol and isopropyl alcohol, depending on factors such as concentration used and packaging conditions Note: Liquids that can easily migrate through the capsule shell are not suitable for soft gelatin capsules. These materials include water above 5% and low molecular weight water-soluble and volatile organic compounds such as alcohols, ketones, acids, amines, and esters. Basic components of soft gelatin capsule shell The various components of the soft gelatin capsule shell are as follows: A. Gelatin Similar to hard gelatin capsule shells, the basic component of soft gelatin capsule shell is gelatin. A large number of different gelatin shell formulations are available depending on the nature of the liquid fill matrix. Most commonly, the gelatin is alkali- (or base-) processed (type B) gelatin and it normally constitutes 40% of the wet molten gel mass. Type A acid-processed gelatin can also be used. The properties of gelatin shells are controlled by the choice of gelatin grade and by adjusting the concentration of plasticizer in the shell. The physicochemical properties of gelatin are controlled to allow 1. Adequate flow at desired temperatures to form ribbons of defined thickness, texture, mechanical strength, and elasticity.
  • 20. 16 2. Ribbons to be easily removed from the drums, stretch during filling, seal the temperature below the melting point of the film, and dry quickly under ambient conditions to an adequate and a reproducible strength. Physicochemical properties of gelatin important to capsule formation include gel strength, viscosity, change in viscosity with temperature and shear, melting point, settling point (temperature), settling time, particle size (affects time to dissolve), and molecular weight distribution (affects viscosity and strength). B. Plasticising agents Plasticizing agents are added in a soft gelatin capsule formulation to ensure adequate flexibility. They interact with gelatin chains to reduce the glass transition temperature (Tg) of the gelatin shell and/or promotes the retention of moisture (hygroscopicity). The most common plasticizer used for soft gelatin capsules is glycerol. Sorbitol, maltitol, and polypropylene glycol can also be used in combination with glycerol. Glycerol derives its plasticizing ability primarily from its direct interactions with gelatin. In contrast, sorbitol is an indirect plasticizer because it primarily acts as a moisture retentive agent. Compared to hard gelatin capsules and tablet film coatings, a relatively large amount (20 -30% w/w) of plasticizers are added in a soft gelatin capsule formulation to ensure adequate flexibility. The amount and choice of the plasticizer contribute to the hardness of the final product and may even affect its dissolution or disintegration characteristics, as well as its physical and chemical stability. C. Water Water usually accounts for 30-40 % of the wet gel formulation and its presence is important both during the manufacturing process (to facilitate manufacture) and in the finished product to ensure that the capsule is flexible. The desirable water content of the gelatin solution used to produce a soft gelatin capsule shell depends on the viscosity of the specific grade of gelatin used. It usually ranges between 0.7 and 1.3 parts of water to each part of dry gelatin. After the capsule is formed, most of the water is removed from the soft gelatin capsules through controlled drying. The finished soft gelatin capsules contain 13– 16 % w/w water, which represents the proportion of water that is bound to the gelatin in the soft gel shell. This level of water is important for good physical stability, because in harsh storage conditions softgels will become either too soft and fuse together, or too hard and embrittled.
  • 21. 17 D. Preservative Preservatives are often added to prevent the growth of bacteria and mould in the gelatin solution during storage. Examples of commonly used as preservatives include potassium sorbate, and methyl, ethyl, and propyl hydroxybenzoate. E. Colorant and/or opacifier A colourant (soluble dyes, or insoluble pigments or lakes) and/or opacifier (e.g., titanium dioxide) may be added to the shell for visual appeal and/or reducing the penetration of light for the encapsulation of a photosensitive drug. The colour of the capsule shell is generally chosen to be darker than that of its contents. F. Other excipients Other, infrequently, used excipients can include flavouring agents and sweeteners to improve palatability. Acid-resistant polymers are used to impart enteric release characteristics. They can also be used to formulate chewable soft gelatin capsules. A chelating agent, such as ethylene diamine tetracetic acid (EDTA), can be added to prevent chemical degradation of oxidation sensitive drugs catalysed by free metals in gelatin, such as iron. Manufacture of Soft Gelatin Capsules Softgels are manufactured using the following methods 1. Plate process 2. Rotary die process 3. Reciprocating die process 4. Accogel process 5. Seamless process Plate process This is the oldest commercial process used in the manufacture of soft gelatin capsules. In this process, a warmed sheet of plain or coloured plasticized gelatin is placed over a die plate having a number of depression or moulds or numerous die pockets. By applying vacuum, the sheet is drawn into these depressions or pockets to form capsule wells. The capsule wells are then filled with medication- containing liquid. A second sheet of gelatin is carefully placed on top of the filled wells followed by the top plate of the mould. Pressure is then applied to the combined plate to form, seal and cut the capsules into individual units. This method is used for small scale preparation of soft gelatin capsules and capsules formed generally, had one flat side.
  • 22. 18 The major problems with this method of manufacturing softgels were the lack of dosage uniformity, high manufacturing losses, and its labour-/cost-intensiveness. This equipment is no longer available. Rotary Die Process Most soft gelatin capsules are prepared by the rotary die process, a method developed and perfected in 1933 by Robert P. Scherer. This process almost eliminated all the problems associated with the plate process and produced soft gelatin capsules with improved uniformity and high standards of accuracy. In this process, two plasticized gelatin ribbons (prepared in the rotary-die machine) are continuously and simultaneously fed with the liquid, semiliquid or paste fill between the rollers of the rotary die mechanism. The forced injection of the feed material between the two ribbons causes the gelatin to swell into the left- and right-hand die pockets which govern the size and shape of the softgels as they converge. As the die rolls rotate, the convergence of the matching dies pockets hermetically seals and cuts out the filled capsules. Softgel formation mechanism (rotary die mechanism) The precise and extremely low clearance of the rotating parts demands continuous lubrication of the machine to avoid even a slight build-up. The lubrication oil should, therefore, be a GRAS (generally recognized as safe) material. Immediately after manufacture, the formed capsules automatically undergo volatile solvent washing to remove any traces of lubricating oil from the exterior of the capsules. The capsules are then conveyed to a drying station and dried on trays, either in air or under vacuum, to equilibrium moisture content to about 6 – 10 % with forced conditioned air of 20% – 30% relative humidity at 21°C–24°C. The drying technique may proceed with an infrared drying step to speed up the process. After drying is complete, capsules are then be transferred to the inspection station and sampled for release, after performing the required quality control tests for
  • 23. 19 sizes sorting, colour sorting, and packaging. Depending on the manufacturer, additional finishing operations such as off-line print can be performed. CONCLUSION Thus at the end I have reach at conclusion that during my one month training in Oxford Pharma, Roorkee Dehradun I have understand the environment of industry and how much company’s staff do the hard work in the production of such a bulk number of product and how one can cope with the problem while working. A pharmaceutical manufacturing unit is placed where not only been best possible formulation are prepared to serve the social surrounding but also industrial training program carried out to prepare technically skilled manufacturing chemist and analysts. In this industry both the above two functions are carried out under the supervision of well skilled experienced and technical persons with complete attention and honesty that improves not only the growth profile of industry but also produce best chemist and analysts in future. I wish for a sharp growth profile of the industry in the coming days and I also admire it to be one of the best places for producing better chemists and analysts beyond the formulation. My opinion about industry is best places are occasionally been noted by someone this is one of them noted by me. I like the environment, staffs and head of departments and heartily wish to work with them ever when an opportunity is given to me.
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