Capsule manufacturing and flowcharts. Capsule ipqc and fpqc

1. M. Pharm Sem-I Presentations
Title:-MANUFACTURING,MANUFACTURING FLOWCHARTAND IPQC OF NON
STARILE DOSAGE FORM-CAPSULE.
SUBMITTED TO
SAVITRIBAI PHULE, PUNE UNIVERSITY , PUNE
FOR
PARTIAL FULFILMENT OF REQUIREMENTS FOR THE AWARD OF
MASTER OF PHARMACY
IN THE SUBJECT
Pharmaceutical Quality Assurance
IN THE FACULTY OF SCIENCE AND TECHNOLOGY
Bhujbal Knowledge City,
MET’s Institute of Pharmacy,
Adgaon, Nashik, 422003.
Maharashtra, India
Academic Year--2021-2022-
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Presented By- Mandlik
Amruta Anil.
Guided By- Dr. Sapna
Ahirrao.

2.  Manufacturing process, manufacturing
flowchart, IPQC of non sterile product:-
Capsule
Contain:-
• Introduction to capsules
• Advantages of capsule
• Disadvantages of capsule
• Manufacturing process and
flowcharts
• In Process Quality Control tests
• Reference
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3. Introduction :-
• Capsules are solid dosage form in which drug substance is
enclosed within hard or soft soluble shell generally formed from
gelatine.
• The term capsule is derived from Latin word Capsula means
small container.
• Capsules may be classified as either hard or soft depending on
nature of capsule shell.
• Soft gelatine capsules are one piece, hermetically sealed, soft
gelatine shell containing liquid, suspension, or semisolid.
• Hard gelatine capsules are of two piece, they are manufactured
and filled in completely separate operations. Hard gelatine
capsules are typically filled with powder, granules, or pellets.
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4. Advantages of capsules:-
• Capsules mask the taste and odour of unpleasant drug and can
be easily administered.
• They are slippery when moist and hence easy to swallow.
• The shells are physiologically inert and easily and quickly
digested in GI track.
• They are economical.
• The shells can be opacified (with titanium dioxide) or coloured
to give protection from light.
• They are easy to handle.
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5. Manufacturing of capsule shells:-
• Hard gelatin capsules are also known as dry filled capsule or
two piece capsule.
• Hard gelatine capsule consist of 2 parts known as capsule body
(longer part) and the capsule cap (shorter part). The drug
substance is placed in the body and the cap is slides over it.
Hence enclosing the drug substance.
• Manufacture:-
The manufacturing equipment consist of pins and pegs made up
of stainless steel to produce the capsule shells of desired shapes
and sizes. About 50 of these pins are attached to the plate which
are movable. Both caps and bodies prepared simultaneously.
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6. Steps:-
1. Dipping:-
Gelatin solution of required viscosity is taken in a
reservoir. The plate holding the pins is lowered into the reservoir
to the suitable depth for the certain period of time. This helps in
achieving proper length and thickness of shells.
2. Drying:-
The plate holding the pins is slowly raised from the
gelatin solution and is subjected to blow drying with air having
controlled temperature and humidity. During this period the
gelatin sets or gels over pins.
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7. 3. Stripping:
The desired capsule shells are then stripped (removed) off
from the pins by using jaws made up of bronze.
4. Trimming:
The stripped capsules shells are then trimmed (shortened)
by stationary knives to the required length.
5. Joining of capsule caps and bodies:
Finally, the trimmed caps and body parts are joined and
released from the machines.
• The width of walls of the capsule shells is to be strictly
controlled for accurate fitting of caps over the bodies.
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9. Manufacturing of Soft gelatin capsules:-
Production by two processes
1.Plate process
2.Rotary or reciprocating die processes
1.Plate process:
It is a semi autonomic process in which a warm sheet of
soft gelatin is laid over a plate having die pockets. Vacuum is
applied from underside of this plate to pull the gelatin sheet into
the pockets. The liquid medication is poured into these dies and
another sheet of soft gelatin of similar or a different color is laid
over it. Finally, a die press which upon application of pressure
seals and cuts off the capsules simultaneously. The capsules are
removed and washed with a volatile solvent. Washing is done to
removed the adhering oil from the capsules.
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10. Manufacturing of Soft gelatin capsules flowchart:-
Spread gelatin sheet over plate having die pocket
Apply vaccum (to create die)
Pour liquid medicament in die
Another sheet of gelatin laid over it
Apply pressure to seal and cut of capsules
Wash with solvents
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11. 2. Rotary Die Process:
This process is developed in the year of 1933. The
capsule prepared by this process have uniformly filled
medications with accurate doses. It is fully automatic continuous
process. Liquid mixture of gelatin is placed in one hopper and
liquid medicament in another hopper. Two rotating dies rotate in
2 opposite direction the fluid gelatin mixture enters into the
machine and produce 2 continuous ribbons. Half shell of capsule
is formed, at this stage the measured quantity of medicament is
filled into it with stroke of pump and subsequent movement of
the dies other half capsule formed. Two half of capsules are
sealed together by the heat and pressure of the rotating dies. As
the die rolls rotate, the convergence of the matching die pocket
seals and cutout the filled capsules.
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13. Flowchart:-
Hopper1 contain gelatin soln.
Gelatin mass spread by gravity
to meter device
Gelatin ribbon of controlled
thickness formed
Ribbon then fed down between
wedge and die rolls
Hopper2 conatain medicament
Laid into the gelatin ribbon in
unit dose
capsule is about half sealed
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14. Cont…
Medicament filled with stock
Subsequent moment of dies form other half capsule
2 half parts of capsule sealed together by heat and pressure
Die pocket seals and cutoff the capsule
Capsules are spread on trays and dry with infrared dryers
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15. IPQC TESTS FOR CAPSULES:-
1. Appearance
2. Size and shape
3. Disintegration test
4. Weight variation
5. Moisture permeation test
6. Bloom strength of gelatine
7. Viscosity and iron content
8. Content uniformity
9. Dissolution test
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16. 1. Appearance:-
• Capsule produced on a small or large scale should be
uniform in appearance. Visual or electronic inspection
should be undertaken to detect any flaws in the integrity
and appearance of the capsule.
• Evidence of physical instability is demonstrated by gross
change in appearance including hardening or softening,
cracking, swelling, mottling, printing mistake, or
discolouration of shell.
• Defective capsules should be rejected.
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17. 2. Size and Shape:-
• Hard capsules are made in a range of sizes, the standard
industrial ones in use today for human medicines range from
size from 000 (the largest, 1.40 ml/ 950 mg) to 5 (the smallest,
0.13ml/ 100 mg) are commercially available.
• 0 to 5 size capsules are for human use.
• Soft gel capsules are available in variety of shapes such as
spherical (0.05-5ml). Ovoid (0.005-7ml). Cylindrical (0.15-
25ml) tubes (0.5-0ml). Pear (0.3-5ml) etc.
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3. Bloom strength of gelatin:-
• Bloom is a test to measure the strength of a gel or gelatin. The
test was originally developed and patented in 1925 by Oscar T.
Bloom.
• The test determines the weight in grams needed by a specified
plunger to depress the surface of the gel by 4 mm without
breaking it at a specified temperature.
• The number of grams is called the bloom value, and most
gelatins are between 30 and 300gm bloom.
• The higher a bloom value, the higher the melting and gelling
points of a gel, and the shorter its gelling times.

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Gelatin bloom tester

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4. Viscosity and iron content:-
• Viscosity of gelatin is measure of molecular chain length and
determines the molecular characteristics of gelatin film.
• Viscosity of 6% gelatin solution is determine in water at 60°C
by measuring the flow time of 100ml of solution through the
standard pipette.
• Viscosity of gelatin range from 25-45 milipoise.
• Iron content: iron content of gelatin use in manufacturing of
capsules, should not contain more than 15ppm.

21. 5. Disintegration test:-
• The USP disintegration apparatus consist of 6 glass tube that are
3 inches long, open at the top, and held against a 10 mesh screen
at the bottom end of the basket rack assembly.
• To test for disintegration time, one capsule is placed in each tube
and the basket rack is positioned in specified medium at 37 ± 2°C
such that capsule remains 2.5cm below the surface of the liquid
on their upward movement and descend not closer than 2.5 cm
from the bottom of the beaker.
• A standard motor driven device is used to move the basket
assembly containing capsules up and down through distance of 5-
6cm at a frequency of 28-32 cycles per minute.
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22. • The capsule complies with the test according to USP if all of
capsules disintegrated completely. If 1 or 2 capsules fails to
disintegrate completely, repeat the test on 12 additional
capsules. The requirement is met if not less than 16 of the total
18 capsules tested are disintegrated according to IP and BP
disintegration time of various capsules are given in table.
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23. • Disintegration time of various capsules according to IP and BP
according to IP disintegration test is not applicable to modified
release capsule.
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Capsule Disintegration
time (min) BP
Disintegration time
(min) IP
Hard capsule 30 30
Soft capsule 30 60
Enteric capsules 60 60
Rectal capsule 30 -

24. • Weigh 20 intact capsules individually and average weight is
determine. Test requirement are met if none of the individual
weights are less than 90% or more than 110% of the average if
the original 20 do not met the criteria the individual weights
are determine this are averaged and the difference are
determine between each individual net content and the
average. The test requirement are met
• 1. if not more than 2 of the individual differences are greater
than 10% of average or
• 2. if in no case any difference is greater than 25%
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6. Weight variation:-

25. • If more than 2 but less than 6 net weights determined by the
test deviate by more than 10% but less than 25% the net
content are determined for additional 40 capsule, and average
calculated for entire 60 capsule. Sixty deviation from new
average is calculated. the requirement are met
• 1 if the difference dose not exceed 10% of average weight in
more than 6 of 60 capsule and
• 2 if in no case any difference exceed 25%
• Two new piece equipment, rotoweigh and vericap 1200,
determined the weight of capsules, providing the automatic
rejection of overfilled and underfilled capsules

26. Average mass (mg) Percentage deviation (%)
Less than 300 10
300 or more 7.5
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IP and BP limits for uniformity of mass:-

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7. Moisture permeation test:-
• The degree and rate of moisture permeation penetration
determine by packaging the dosage unit together with a color
reveling desiccant pellet.
• Expose the packaged unit to known relative humidity over a
specified time.
• Observe the desiccant pallet for color change.
• Any change in color indicates absorption of moisture.
• By measuring pre test and protest weight of pellet amount can
be calculated.

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8. Content uniformity:-
• As per USP and BP
• Select randomly 30 capsule (soft or hard) 10 of which are
assayed by specified procedure.
• The requirements are met if 9 of the 10 are within specified
potency range of 85 to 115% and 10th is not outside 75 to
125% .
• If more than 1, but less than 3,of first 10 capsule fall outside
the 85 to 115% limits, the remaining 20 capsule are assayed.
• The requirement are met if all 30 capsule are within 75 to
125% of specified potency range,and not less than 27 of the 30
are within the 85 to 115% range.

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9. Dissolution test :-
• Dissolution test is carried out using dissolution apparatus
official in both USP and IP
• The capsule is placed in basket and basket immersed in
dissolution medium and temperature is maintained at 37°c±5°c
• 6 capsule are tested and accepted if each of them is not less
than monograph specified i.e.. Q±5. if it fails additional 6
capsules are tested the result is accepted if avg. of 12 capsule
is greater than or equal to Q and none of them is less than Q-
15.
• If capsule still fails the test additional 12 capsules are tested
and are accepted if the avg. of 24 is greater than Q, if not more
than 2 less than Q-15% and none of them is less than Q-25%

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Acceptance table
Stage Number of capsules Acceptance criteria
S1 6 Each unit is ≥Q+5%
S2 6 Average of 12 units is ≥ Q, NMT 2 units
are < Q-15%
S3 12 Average of 24 units is ≥Q, NMT 2 units
are <Q-15% and no single unit is less
than Q-25%.

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 Reference:-
1. L. Lachman, HA Lieberman, JL Kanig. The Theory and Practice of Industrial
Pharmacy, 3rd Edition, Lea AND Febiger, Philadelphia, 1986, 374-398.
2. Indian Pharmacopoeia Commission. Indian Pharmacopoeia. 7th ed.
Ghaziabad: Indian Pharmacopoeia Commission : 2014.
3. United States Pharmacopeial Convention. United Stated Pharmacopoeia
33- National Formulary 28. USA : Stationary office; 2010.
4. British Journal of Pharmaceutical Research 9(2); 1-9, 2016, article no.
BJPR 22044 ISSN; 2231-2919.

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