Inprocess as per usp ip bp capsule

1. CAPSULE
General chapter

2. General introduction
• 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.
• Excipients such as opaque fillers, antimicrobial preservatives, sweetening agents,
flavoring agents and one or more coloring 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 coloring agent.

3. CAPSULES• solid dosage form
• the drug is enclosed within either a hard or
soft shell
– shell is typically made of gelatin
• primarily intended for oral delivery
• provide a rapid release of contents
B. Amsden 3CHEE 440

4. Filling
• operations involved
– rectification of empty capsules
– separation of caps from bodies
– filling capsule bodies
– replacing caps and ejecting filled capsules
• 3 basic methods for powder filling
– auger or screw
– dosator
– dosing disc
B. Amsden 4CHEE 440

5. Capsule Filling
– auger
• semi-automatic operation
• filling based on volume
• need good powder flow properties
– dosator
• fill based on weight
• continuous operation
B. Amsden 5CHEE 440

6. Capsule Filling– dosing disc
• filled based on weight
• continuous operation
B. Amsden 6CHEE 440

7. Hard Gelatin Capsules
• Advantages
– tasteless and odourless
– swallowing is easy
– flexibility in formulating
– uniquely suitable for blinded clinical trials
– useful for extemporaneous compounding by
pharmacist
• Disadvantages
– tend to be more expensive to produce than tablets
– not suitable for highly soluble salts
B. Amsden 7CHEE 440

8. Different size of hard gelatin capsule

9. Soft Gelatin Capsules (Softgels)
• consist of a continuous gelatin shell surrounding a liquid core
• formed, filled, and sealed in one operation
• shells are softened by addition of glycerin or polyhydric
alcohol (ex. sorbitol)
• oblong, spherical, elliptical in shape
B. Amsden 9CHEE 440

10. Manufacture
B. Amsden 10CHEE 440

11. Soft Capsules
• ADVANTAGES
– may contain liquids, suspensions, pastes
– rapid release of contents
– useful for drugs prone to oxidation
• DISADVANTAGES
– have a greater tendency to adhere to each other
– more expensive
– increased possibility of interactions between drug
and shell
B. Amsden 11CHEE 440

12. Types of capsule
• Hard Gelatin Capsules
• Soft Gelatin Capsules
• Modified-release Capsules
• Enteric Capsules

13. Tests
• Uniformity of container contents
• Content of active ingredients
• Uniformity of content
• Uniformity of weight
• Dissolution
• Disintegration (not applied for
• modified release capsule)
• Leak test
• Locking length
Pharmacopoial
Non- Pharmacopoial

14. Uniformity of container contents /
Contents of Packaged Dosage Forms (IP)
• The following tests and specifications apply to oral dosage forms and
preparations intended for topical use that are packaged in containers in
which the labeled net quantity is not more than 100 g or 300 ml or 1000
units, as the case may be
• For higher labeled quantities the test and limits given in the standards of
Weights and Measures (Packaged commodities) Rules, 1977 may be
followed.

15. Contents of Packaged Dosage Forms
• Test Method
• Select a sample of 10 containers and count the number of capsules in each
container.
• The average number of the contents in the 10 containers is not less than the
labeled amount and the number in any single container is not less than 98 per
cent and not more than 102 per cent of the labeled amount
• If this requirements is not met, count the number of the contents in 10
additional containers. The average number in the 20 containers is not less
than the labeled amount, and the number in not more than 1 of the 20
containers is less than 98 per cent or more than102 per cent of the labeled
amount.

16. • This test is applicable to capsule that contain less than 10 mg or less than 10
per cent w/w of active ingredient (As per IP).
• This test is applicable to capsule that contain less than 25 mg or less than 25
per cent w/w of active ingredient (As per BP/USP ).
• For capsule containing more than one active ingredient carry out the test for
each active ingredient that corresponds to the aforementioned conditions.
• The test for Uniformity of content should be carried out only after the content
of active ingredient(s) in a pooled sample of the capsule has been shown to be
within accepted limits of the stated content.
• The test for Uniformity of content is not applicable to capsule containing
multivitamins and trace elements.
Uniformity of contant (IP)

17. • The test for uniformity of content of single-dose preparations is based on the assay
of the individual contents of active substance(s) of a number of single-dose units
to determine whether the individual contents are within limits set with reference to
the average content of the sample.
• Method.
• Determine the content of active ingredient(s) in each of 10 dosage units taken at
random using the method given in the monograph or by any other suitable
analytical method.
• Acceptance limits
• The preparation complies with the test if not more than one individual content is
outside the limits of 85 to 115 per cent of the average content and none is
outside the limits of 75 to 125 per cent of the average content.
• The preparation fails to comply with the test if more than three individual
contents are outside the limits of 85 to 115 per cent of the average content or if
one or more individual contents are outside the limits of 75 to 125 per cent of the
average content.
Uniformity of content (IP)

18. • If two or three individual contents are outside the limits of 85 to 115 per cent
of the average content but within the limits of 75 to 125 per cent, repeat the
determination using another 20 dosage units.
• The preparation complies with the test if not more than three individual
contents of the total sample of 30 dosage units are outside the limits of 85 to
115 per cent of the average content and none is outside the limits of 75 to 125
per cent of the average content.
Uniformity of contents

19. Uniformity of Weight of Single-Dose
Preparations (IP/BP)
• 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 shown in the table
and none deviates by more than twice that percentage.

21. Disintegration Test
• For the purpose of this test, disintegration does not imply complete
solution of the dosage unit or even of its active constituent.
• Disintegration is defined as that state in which no residue of the unit
under test remains on the screen of the apparatus or, if a residue
remains, it consists of fragments of disintegrated parts of capsule
component parts such as insoluble coating of the of capsule shells, or
of any melted fatty substance from the pessaries or suppository or is a
soft mass with no palpable core.
• If discs have been used with capsules, any residue remaining on the
lower surfaces of the discs consists only of fragments of shells.
• 28-32 cycle (strokes) per minute IP
• 29-32 cycle (strokes) per minute BP/USP

22. Method
• Unless otherwise stated in the individual monograph, introduce one
capsule into each tube and, if directed in the appropriate general
monograph, add a disc to each tube. Suspend the assembly in the beaker
containing the specified liquid and operate the apparatus for the
specified time.
• Remove the assembly from the liquid. The capsules pass the test if all of
them have disintegrated.
• If 1 or 2 capsules fail to disintegrate, repeat the test on 12 additional
capsules; not less than 16 of the total of 18 capsules tested disintegrate.
• If the capsules adhere to the disc and the preparation under
examination fails to comply, repeat the test omitting the disc. The
preparation complies with the test if all the capsules in the repeat test
disintegrate.

23. For enteric-coated capsule
• Method.
• If capsule having soluble external sugar coating, immerse the basket in
water at room temp for 5 min (USP).
• Put one capsule into each tube, suspend the assembly in the beaker
containing 0.1M hydrochloric acid and operate without the discs for (2
hour as per IP/BP) (1 hour as per USP) , unless otherwise stated in the
individual monograph. Remove the assembly from the liquid.
• No capsule shows signs of cracks that would allow the escape of the
contents or disintegration, apart from fragments of coating.
• Replace the liquid in the beaker with mixed phosphate buffer pH 6.8, add
a disc to each tube and operate the apparatus for a further 60 minutes.
• Remove the assembly from the liquid. If the capsule fails to comply
because of adherence to the disc, repeat the test on a further 6 capsule
without the discs. The capsule pass the test if all six have disintegrated.

24. Disintegration testing condition and interpretation (IP)
Sr.
No
Type of capsule Medium Temperatu
re
Limit
1 Hard gelatin Water/buffer 37 °± 2 °C 30 min or as per individual
monograph
2 Soft gelatin Water 37 °±2 °C 60 min or as per individual
monograph
3 Enteric-coated 0.1 M HCl
mixed
phosphate
buffer pH 6.8
37 °±2 °C 02 hour in HCl: no disintegration
60 min in buffer : disintegrate

25. Disintegration testing condition and interpretation (BP)
Sr.
No
Type of capsule Medium Temperatu
re
Limit
1 Hard gelatin Water/0.1 M
HCl/ Artificial
gastric juice R
37 °± 2 °C 30 min or as per individual
monograph
2 Soft gelatin Water/0.1 M
HCl/ Artificial
gastric juice R
37 °±2 °C 60 min or as per individual
monograph
3 Enteric-coated 0.1 M HCl
mixed
phosphate
buffer pH 6.8
37 °±2 °C 02 hour in HCl: no disintegration
60 min in buffer : disintegrate

26. Disintegration testing condition and interpretation (IP)
Sr.
No
Type of capsule Medium Temperatu
re
Limit
1 Hard gelatin Water/buffer 37 °± 2 °C 30 min or as per individual
monograph
2 Soft gelatin Water 37 °±2 °C 60 min or as per individual
monograph
3 Enteric-coated 0.1 M HCl
mixed
phosphate
buffer pH 6.8
37 °±2 °C 02 hour in HCl: no disintegration
60 min in buffer : disintegrate

27. Dissolution Test
• Use Apparatus 1 unless otherwise directed.
• Use the dissolution medium specified in
• the individual monograph. If the medium is a buffered
solution, adjust the solution so that its pH is within 0.05
units of the pH specified in the monograph.
• Time. Where a single time specification is given in
the monograph, the test may be concluded in a shorter
period if the requirement for the minimum amount
dissolved is met. If two or more times are specified,
specimen are to be withdrawn only at the stated times,
within a tolerance of ± 2 per cent.

28. • Assemble the apparatus and warm the dissolution
medium to 36.5 ° to 37.5 °C unless otherwise stated
• Within the time interval specified, or at each of the
times stated, withdraw a specimen from a zone midway
between the surface of the dissolution medium and the
top of the rotating blade or basket, not less than 10 mm
from the wall of the vessel.
• Except in the case of single sampling, add a volume of
dissolution medium equal to the volume of the samples
withdrawn.
• Perform the analysis as directed in the individual
monograph.

29. Acceptance criteria
Conventional-release dosage forms (IP)
• Unless otherwise specified, the requirements are met if the quantities of
active substance dissolved from the dosage units conform to Table
below . If the results do not conform to the requirements at stage S1
given in the table, continue testing with additional dosage units through
stages S2 and S3 unless the results conform at stage S2.
• Where capsule shells interfere with the analysis, remove the contents
of not less than 6 capsules as completely as possible, and dissolve the
empty capsule shells in the specified volume of the dissolution
medium.
• Perform the analysis as directed in the individual monograph. Make
any necessary correction.
• Correction factors should not be greater than 25 per cent of the stated
amount.

30. As per IP

31. Acceptance criteria
• Conventional-release solid dosage forms (BP/USP)
• Unless otherwise specified, the requirements are met if
the quantities of active substance dissolved from the
dosage units tested conform to Table below. Continue
testing through the 3 levels unless the results conform
at either S1 or S2.
• The quantity Q, is the specified amount of dissolved
active substance, expressed as a percentage of the
labeled content; the 5 per cent, 15 per cent, and 25 per
cent values in the Table are percentages of the labeled
content so that these values and Q are in the same
terms.

32. As per (BP/USP)

33. Prolonged-release dosage forms (IP)
• Unless otherwise specified, the requirements are met if
the quantities of active substance dissolved from the
dosage units conform to Table below.
• If the results do not conform to the requirements at stage
L1 given in the table, continue testing with additional
dosage units through stages L2 and L3 unless the results
conform at stage L2.
• The limits embrace each value of D, the amount dissolved
at each specified dosing interval.
• Where more than one range is specified, the acceptance
criteria apply to each range.

35. Prolonged-release dosage forms
(BP/USP)
• Unless otherwise specified, the requirements are met if
the quantities of active substance dissolved from the
dosage units tested conform to Table below.
• Continue testing through the 3 levels unless the results
conform at either L1 or L2.
• Limits on the amounts of active substance dissolved are
expressed in terms of the percentage of labeled
content. The limits embrace each value of Qi, the
amount dissolved at each specified fractional dosing
interval. Where more than one range is specified, the
acceptance criteria apply individually to each range.

37. Modified-release dosage forms (IP)
There are 2 method A & B
Method A & B
Acid stage.
• 750 ml/1000 ml of 0.1M hydrochloric acid
• 36.5º to 37.5º.
• 2 hours
• Perform the analysis of the aliquot using a suitable assay method.
Buffer stage.
• Complete the operations of adding the buffer and adjusting the pH within 5
minutes.
• 250 ml of a 0.2 M buffer and solution
• 36.5º to 37.5º.
• 6.8 ± 0.05
• 45 minutes, or for the specified time.

38. Acceptance criteria (IP)
• ACID STAGE
• The requirements of the test are met if conform to Table below.
Continue the testing through the 3 levels unless the results of
both acid and buffer stages conform at an earlier level

39. Acceptance criteria (IP)
• BUFFER STAGE
• The requirements of the test are met if conform to Table below.
Continue the testing through the 3 levels unless the results of both acid
and buffer stages conform at an earlier level
• The value of D in Table is 75 per cent dissolved unless otherwise
specified.
• The quantity, D, is the specified total amount of active substance
dissolved in both the acid and buffer stages, expressed as a percentage
of the labeled content.

40. Prolonged-release solid dosage forms
(BP/USP)
There are 2 method A & B
Method A & B
Acid stage.
• 750 ml/1000 ml of 0.1M hydrochloric acid
• 36.5º to 37.5º.
• 2 hours
• Perform the analysis of the aliquot using a suitable assay method.
Buffer stage.
• Complete the operations of adding the buffer and adjusting the pH within 5
minutes.
• 250 ml of a 0.2 M buffer and solution
• 36.5º to 37.5º.
• 6.8 ± 0.05
• 45 minutes, or for the specified time.

41. Acceptance criteria (BP/USP)
• ACID STAGE
• Unless otherwise specified, the requirements of this portion of the test are
met if the quantities, based on the percentage of the labeled content of
active substance dissolved from the units tested conform to Table 2.9.3.-3.
Continue testing through the 3 levels unless the results of both acid and
buffer stages conform at an earlier level.

42. Acceptance criteria (BP/USP)
• BUFFER STAGE
• The requirements are met if active substance dissolved from the units tested
conform to Table 2.9.3.-4.
• Continue testing through the 3 levels unless the results of both stages conform at
an earlier level.
• The value of Q in Table 2.9.3.-4 is 75 per cent dissolved unless otherwise specified.
• The quantity, Q, is the specified total amount of active substance dissolved in
both the acid and buffer stages, expressed as a percentage of the labeled
content.
• The 5 per cent, 15 per cent and 25 per cent values in the Table are percentages of
the labeled content so that these values and Q are in the same terms.

43. Dissolution testing condition and interpretation (IP)
Sr.
No
Type of capsule Medium Temperature Limit
1 Hard gelatin Water/buffer 37 °± 5 °C As per tables shown before or As
per individual monograph
2 Soft gelatin Water 37 °±5 °C As per tables shown before or As
per individual monograph
4 Enteric-coated
capsule
0.1 M HCl &
Mixed
phosphate
buffer pH 6.8
37 °±2 °C 02 hour in HCl & 60 min in buffer
As per tables shown before or As
per individual monograph

45. Defects of capsules