In-Process AND Finished Products Quality Control Tests of Capsules

A REPORT ON
A REPORT ON
IN-PROCESS
IN-PROCESS
AND
AND
FINISHED
FINISHEDPRODUCTS
PRODUCTS
QUALITY
QUALITYCONTROL
CONTROLTESTS
TESTS
OF
OFCAPSULES
CAPSULES
SUBMITTED BY:
LIPIMUDRA PADHY
REGD. NO.: 11902184
LOVELY PROFESSIONAL UNIVERSITY, PHAGWARA, PUNJAB, INDIA

CONTENTS
• Introduction
• Types
• Structure and size
• Tests under Indian Pharmacopoeia
• Tests under British Pharmacopoeia
• Tests under United States Pharmacopoeia
2
INTRODUCTION:
• A solid dosage form containing drug or mixture of drugs

• Mostly enclosed in hard or soft gelatin shells
• Can contain a single or more than one active substances
• Generally, intended for oral administration
• Also can be used as dry powder inhalers, suppositories, etc.
• Capsule shells are filled with powder, granules, pellets, beads, tablets, paste,
liquid or paste-like consistency
• Contents should not deteriorate the capsule shells
• May or may not contain excipients permitted under Drug and Cosmetics Rules,
1945
• Glycerin and sorbitol maintains consistency of soft shells
3
INTRODUCTION:
• A solid preparation containing single dose of active substance(s)

• Consisting of hard or soft shells of various shapes and sizes
• Generally, intended for oral administration
• Contents of capsules may be solid, liquid or paste-like consistency
• Consisting of one or more active substances with or without excipients
• Capsule shells are made up of gelatin
• Glycerol and sorbitol maintains the consistency of shells
• Contents do not cause deterioration of capsule shells
4
TYPES OF CAPSULES
HARD GELATIN CAPSULES SOFT GELATIN CAPSULES

• Shells containing two prefabricated, cylindrical • Capsule shells are usually formed, filled with
sections medicament and sealed
• One end is closed and rounded and other one is • For extemporaneous use, capsule shells may be
open prefabricated
• Contents are filled in form of powders, granules • Shells are made thicker to produce capsules
or pellets, semisolids or liquids, etc. which are spherical, oval and cylindrical with
• Contents are filled in one section and the other hemispherical ends
section is closed over by closure • Liquid medicaments are enclosed directly,
• Shells are prepared by dipping shaped pins into while solids are dissolved or dispersed in a
gelatin suitable vehicle to get paste like consistency
5
NEWER TYPES OF CAPSULES
• Modified-release capsules
• Prolonged release capsules
• Gastro-resistant capsules
• Hard cellulose capsules
• Cachets
• Gelatin-free soft capsules
• Softlet® gel capsules
• Liquid filled hard gelatin capsules
• Rectal capsules
• Capsules for packing of ophthalmic ointments
• New soft-gel variants
• Enteric soft gel
• Controlled release soft gel
• Chewable soft gel 6
STRUCTURE AND SIZES OF CAPSULES
Table-1 Sizes of Capsules
External
Locked length
Sizes Volume (ml) diameter
(mm)
(mm)
5 0.13 11.1 4.91
4 0.20 14.8 5.31
3 0.27 15.9 5.82
2 0.37 18 6.35
1 0.48 19.4 6.91
0 0.67 21.7 7.65
00 0.95 23.3 8.53
000 1.36 26.14 9.91
Fig. 1 Structure of Capsule
7
UNITED STATES INDIAN
PHARMACOPOEIA PHARMACOPOEIA
(USP) (IP)
IN-PROCESS
AND
FINISHED PRODUCTS
QUALITY CONTROL TESTS
BRITISH
PHARMACOPOEIA
(BP)
8
INDIAN PHARMACOPOEIA
Content of
active Dissolution
ingredients test
Uniformity Disintegration
of weight test
Uniformity
of content
9
INDIAN PHARMACOPOEIA CONTENT OF ACTIVE INGREDIENTS
• Determination of active ingredient(s) in each capsule by assay method
• Result must lie within the range stated in the monograph
• Range is based on 20 capsules or such numbers as indicated in monograph
• Less than 5 capsules cannot be used
• Limits are between 90 and 110 percent for requirements of table-2
• Deviation from this limits needs smaller or larger allowances
Table-2
Subtract from the lower limit for Add to the upper limit for the
Weight of active ingredients in each the samples of samples of
Capsules
15 10 5 15 10 5
0.12 g or less 0.2 0.7 1.5 0.3 0.8 1.8
More than 0.12 g and less than 0.3 g 0.2 0.5 1.2 0.3 0.6 1.5
0.3 g or more 0.1 0.2 0.8 0.2 0.4 1.0

10
INDIAN PHARMACOPOEIA UNIFORMITY OF WEIGHT
• Determination of variation of weights in contents of capsule
• 20 capsules are taken and weighed individually
Table-3
• For hard gelatin capsules,
• Open the shell Average weight
of Percentage deviation
• Remove carefully the contents completely capsule contents
• For soft gelatin capsules,
Less than 300 mg 10
• Shell washed with ether
300 mg or more 7.5
• Stand until the odour of solvent is no longer detectable
• Shell is weighed
• Difference is based on the weight of contents
• Acceptance criteria
• Not more than 2 capsules should deviate from average weight by more than the
percentage deviation
• None of the capsule must deviate more than twice the percentage deviation
11
• Percentage deviation is mentioned in table-3
INDIAN PHARMACOPOEIA UNIFORMITY OF CONTENT
• Test is done for capsules containing less that 10 ml or 10%w/w of active ingredient
• Test for each ingredient is done if more than one active ingredient is present
Randomly take 10 capsules and determine active ingredient content
If not more than one values obtained is outside the limits

85-115% of average value
And
If no value is outside the limits 75-125% of average value
Passes Fails
If in all 30 capsules, not more than three
Repeat using Passes individual values are outside the limits 85-
Test passes 115% and none of the individual values are
another 20 capsules
outside the limits 75-125% of the average
value
12
INDIAN PHARMACOPOEIA DISINTEGRATION TEST
• Determines whether dosage form disintegrate in prescribed time and

liquid medium under prescribed experimental conditions
• Two Basket-rack assembly apparatus are used:
• Apparatus A: capsules of not more than 18 mm long
• Apparatus B: capsules of more than 18 mm long
• Apparatus A specifications:
• Consist of six cylindrical glass tubes (77±2.5 mm long, 21.5
mm internal diameter and 2 mm wall thickness) held vertically
by two transparent plastic plates (90±2 mm in diameter and
6.75±1.75 mm thick)
• The underside of the tubes have woven stainless steel wire cloth
with 2.0±0.2 mm mesh apertures and wire diameter of
0.615±0.045 mm
• The tubes are covered with plastic plates of diameter 24±2 mm.
• A vertical metal rod is attached at center for raising and
lowering the assembly
• Frequency is between 29-32 cycles per minute through a Fig. 2 Disintegration test Apparatus A
distance of 55±2 mm (Dimensions in mm)
13
• A cylindrical disc each of 20.7±0.15 mm in diameter and 9.5±0.15 mm thick, made of transparent plastic (relative
density 1.18 to 1.20)
• Disc have five holes (2mm diameter), one at center and other four spaced equally on circle of radius 6 mm from
center
• Four equal spaced grooves are made on lateral surface so that at the upper surface, 9.5 mm wide and 2.55 mm
deep and at lower surface, 1.6 mm
• Assembly is suspended in a suitable medium filled beaker of 1 litre
• Volume of liquid should be such that wire mesh at highest point is atleast below 15 mm below surface of the
liquid and 25 mm above the bottom of the beaker
• Thermostatic arrangement for heating and maintaining temperature of the medium at 37±2°C
14
• Apparatus B specifications:
• Consist of three cylindrical glass tubes (77.5±2.5 mm long, 33±0.5
mm internal diameter and 2.5±0.5 mm wall thickness)
• Tubes are held vertically by two rigid plastic plates (97 mm in
diameter and 9 mm thick)
• The underside of the tubes have woven stainless steel wire cloth with
0.63±0.03 mm mesh apertures and wire diameter of 2.0±0.2 mm
• A vertical metal rod is attached at center for raising and lowering the
assembly
• Frequency is between 29-32 cycles per minute through a distance of
55±2 mm
• A cylindrical disc each of 31.4±0.13 mm in diameter and 15.3±0.15
mm thick, made of transparent plastic (relative density 1.18 to 1.20)
• Disc have seven holes 3.15±0.1 mm in diameter, one at center and
other six spaced equally on circle of radius 4.2 mm from center
• Assembly is suspended in a suitable medium filled beaker of 1 litre
• Volume of liquid should be such that wire mesh at highest point is
atleast below 15 mm below surface of the liquid and 25 mm above
the bottom of the beaker
Fig. 2 Disintegration test Apparatus B
• Thermostatic arrangement for heating and maintaining temperature
(Dimensions in mm)
of the medium at 35-39°C 15
• Operation time (if not specified): Hard gelatin capsules (30 mins) and Soft gelatin capsules (60 mins)
• Method:
• Introduce one capsule in each glass tube
• Suspend the beaker into the specified medium for specified time
• Test passes if all six capsules disintegrate
• If one or two capsules does not disintegrate completely,
• Repeat taking another 12 capsules
• Passes if 16 of the total 18 capsules disintegrate
• Gastro-resistant capsules:
• Operated for 2 hours taking 0.1 M hydrochloric acid as the medium
• No disintegration should take place
• Replace the medium with mixed phosphate buffer pH 6.8
• Operated for 60 minutes
16
INDIAN PHARMACOPOEIA DISSOLUTION TEST
• An in-vitro test for determining the release profile of

active ingredient
• Four types of apparatus are used for capsules:
• Apparatus 1: Paddle Apparatus
• Apparatus 2: Basket Apparatus
• Apparatus 3: Reciprocating Cylinder
Fig. 3 Apparatus 1 Fig. 4 Apparatus 2
• Apparatus 4: Flow-through Cell
• The test methods differs depending upon the dosage form
Fig. 5 Apparatus 3 Fig. 6 Apparatus

17 4
• Methods and Acceptance criteria:
1. Apparatus 1 and Apparatus 2: Table-4
• For conventional and prolonged-release solid dosage form: Number
Level Acceptance criteria
tested
• Place the dissolution medium and maintain temperature at
Each unit is not less than
36.5° to 37.5°C S1 6
D*+5%**
• Introduce capsule directly into vessel and wait until it sinks Average of 12 units
(Apparatus 1) or in basket (Apparatus 2) (S1+S2) is equal to or
S2 6
greater than D, and no unit
• Operate at speed of rotation mentioned in monograph is less than D-15%**
• Withdraw specimen at specified time period Average of 24 units
• For each capsule, the amount of active ingredient in solution (S1+S2+S3) is equal to or
greater than D, not more
S3 12
is calculated as the percentage of the stated amount than 2 units are less than
D-15%** and no unit is less
• The requirements are met if the quantity of the active than D-25%**
ingredient dissolved relies to table-4 and table-5.
*D is the amount of dissolved active ingredient specified in the
• For conventional dosage form, if results does not relies at individual monograph, expressed as the % of the labelled content
**Percentage of labelled content 18
stage S1, carry out stage S2 and S3
• For prolonged release dosage form, if results does not relies at stage L1, carry out stage L2 and L3 until it conform
with L2
Table-5
Level Number tested Acceptance criteria
No individual values lie outside each of the stated ranges and no
L1 6
individual value is less than the stated amount at the final test time.
The average value of the 12 units (L1+L2) lies within each of the
stated ranges and is not less than the stated amount at the final test
L2 6 time; none is more than the 10% of the labelled content outside each
of the stated ranges; and none is more than 10% of the labelled
amount below the stated amount at the final test time.
The average value of the 24 units (L1+L2+L3) lies within each of the
time; not more than 2 of the 24 units are more than 10% of the
labelled content outside each of the stated ranges; not more than 2 of
L3 12
the 24 units are more than 10% of the labelled content below the
stated amount at the final test time; and none of the units is more than
20% of labelled content outside each of the stated ranges or more than
20% of labelled content below the stated amount at the final test19 time.
1. Apparatus 1 and Apparatus 2:
• For modified release solid dosage form: Two methods are used; Method A or Method B
Table-6
Method A Method B
• Acid stage
• Acid stage
• 1000 ml of 0.1M Hydrochloric acid
• Warm to 36.5°-37.5°C
• Warm to 36.5°-37.5°C
• Operate at specified rate for 2 hours
• Operate at specified rate for 2 hours
• Collect an aliquot and analyse by suitable assay method
• Continue in buffer stage
• Buffer stage
• Buffer stage
• 1000 ml of pH 6.8 phosphate buffer (3 volumes of 0.1 M
• Adjust the pH within 5 minutes
hydrochloric acid and 1 volume 0.2 M trisodium
• Add 250 ml of 0.2 M solution of trisodium phosphate
phosphate dodecahydrate) warmed at 36.5°-37.5°C
dodecahydrate warmed at 36.5°-37.5°C
• Adjust pH to 6.8±0.05 with 2 M hydrochloric acid or 2 M
sodium hydroxide
sodium hydroxide
• Operate for 45 minutes or as specified in monograph
• Withdraw specimen at the end of time period and analyse
by suitable assay method
20
• Acid stage: The requirements of this part of the test is met if the quantities of the labelled content of active
substance tested conform to table-7
• Buffer stage: The requirements of this part of the test is met if the quantities of the labelled content of active
Table-7
Table-8
Number
Level Acceptance criteria Number
tested a Acceptance criteria
tested
No individual value exceed 10%
A1 6
dissolved B1 6 No unit is not less than D+5%**
Average of 12 units (A1+A2) is
Average of 12 units (B1+B2) is
not more than 10% dissolved and
A2 6 B2 6 equal to or greater than D, and no
no individual unit is greater than
unit is less than D-15%**
25% dissolved
Average of 24 units (A1+A2+A3) Average of 24 units (B1+B2+B3)

is not more than 10% dissolved is equal to or greater than D, not
A3 12 B3 12 more than 2 units are less than D-
and no individual unit is greater
than 25% dissolved 15%** and no unit is less than D-
25%** 21
2. Apparatus 3:
• For conventional and prolonged release dosage form:
• Place the dissolution medium and maintain temperature at 36.5° to 37.5°C
• Introduce capsule directly into each of the six reciprocating cylinders
• Operate as mentioned in monograph
• Reciprocating cylinder moves a distance of total 9.9-10.1 cm
• Withdraw specimen at specified time period by raising the reciprocating cylinders
• For each capsule, the amount of active ingredient in solution is calculated as the percentage of the stated amount
• For modified release dosage form:
• Same as Method B described in Apparatus 1 and Apparatus 2 for acid stage
• Follow one row of vessels
• Change the volume of medium in buffer stage to 250 ml
22
3. Apparatus 4:
• Place the glass beads into the cell
• Place one capsule at the top of the bead
• Assemble the parts together with clamping device
• Allow dissolution medium by pump through bottom of cell, warmed at 36.5° to 37.5°C
• Withdraw specimen by fractions at specific time
• For modified release dosage form:
• Same as described in Apparatus 1 and Apparatus 2 using specified media
23
UNITED STATES PHARMACOPOEIA
Disintegration Dissolution
test test
24
UNITED STATES PHARMACOPOEIA
DISINTEGRATION TEST
• Defined as the state where residue of unit except fragments of insoluble coating or capsule shells,
remaining on the screen of test apparatus
• Specifications of the assembly:
• Basket rack assembly (1000 ml)
• Low form beaker
• 6 tubes with a wire cloth of diameter 0.57-0.66 mm
• 138-160 mm height
• 97-115 mm diameter for immersion fluid
• Thermostatic arrangement between 35º and 39º
• Frequency rate between 29 and 32 cycles per minute
• Distance of not less than 53 mm and not more than 57 mm
• Volume of the fluid in vessel: Upward stroke height remains 15 mm below the fluid surface and
Downward stroke descends to not less than 25 mm from bottom of vessel
• Vertical movement of the assembly along its axis
25
UNITED STATES PHARMACOPOEIA DISINTEGRATION TEST PROCEDURE
Place 1 dosage unit in each tube and add a

disk
Fill with water or specific medium as the immersion fluid
Maintain the temperature at 37±2°C and operate the apparatus
Observe the capsules for the time specified in

monograph
Capsules have disintegrated except the capsule shells
Repeat tests for 12 additional Not fewer than 16 of the total

capsules if 1 or 2 capsules fail 18 capsules tested should
to disintegrate completely disintegrate completely
26
UNITED STATES PHARMACOPOEIA DISSOLUTION TEST
• Test for determining the compliance of solid dosage form with

the dissolution requirements
Fig. 7 Apparatus 1 Fig. 8 Apparatus 2
Fig. 9 Apparatus 3 Fig. 10 Apparatus

27 4
APPARATUS 1: BASKET APPARATUS
28
• It consists of: a vessel, a motor, a metallic drive shaft and a
cylindrical basket
• Vessel is partially immersed in water bath that contains a
heating device to keep the temperature inside vessel at
37±0.5°C
• Vessel:
• Cylindrical, hemispherical end and flanges sides at top
• Dimension and capacities of either of the following:
Capacity of 1L (160-210 mm height and 98-106 mm
inside diameter); Capacity of 2L (280-300 mm height
and 98-106 inside diameter) and Capacity of 4L (280-300
mm height and 145-155 mm inside diameter)
• A cover used to retard evaporation
• Shaft is positioned vertically from axis at not more than 2 mm
from any point of the vertical axis of vessel and rotated
smoothly
• A speed regulating device regulates and maintains speed of
shaft according to monograph within ±4%
• Shaft and basket are made of type 316, stainless steel and
basket have gold coating of 2.5µm thick
• The distance between bottom of vessel and bottom of basket is Fig. 11 USP Apparatus 1 Basket Apparatus
29
maintained at 25±2 mm during test
APPARATUS 2: PADDLE APPARATUS
30
• It consists the same assembly as
Apparatus 1 except the paddle formed
from a blade and a shaft
• Paddle:
• A two-part detachable design that
firmly remains engaged during the
test
• Made up of inert material
• Shaft is positioned vertically from axis at
not more than 2 mm from any point of
the vertical axis of vessel and rotated
smoothly
• Dosage unit is allowed to sink to the Fig. 12. a. Alternative Sinkers
bottom before the paddle rotates (dimensions in mm)
• If it is floating, few turns of wire helix
(sinker) is used to keep it at the bottom
• The distance between bottom of vessel
and bottom of paddle is maintained at
25±2 mm during test
Fig. 12 USP Apparatus 1 Paddle Apparatus
31
APPARATUS 3: RECIPROCATING CYLINDER
32
• It consists of:
• Set of cylindrical, flat-bottomed glass vessels
• Set of glass reciprocating cylinders
• Inert fittings made of type 316, stainless steel
• Screens are made of non-absorbing and non-reactive material
and are designed to fit the tops and bottoms of reciprocating
cylinder
• A motor and drive assembly to reciprocate the cylinder
vertically inside the vessels
• Vessels are partially immersed in a water bath having a heating
device that maintains the temperature of 37±0.5°C during the test
• Due to smooth, vertically reciprocating cylinders, no vibrations or
agitations should be present neither in the environment nor in the
assembly
• A device used to regulate and maintain the reciprocation rate
mentioned in the specific monograph within ±5%
• Vessels are provided with evaporation cap that retard the
evaporation
Fig. 13 USP Apparatus 3

33
Reciprocating Cylinder
APPARATUS 4: FLOW THROUGH CELL
34
• It consists of:
• A reservoir and a pump for the dissolution medium
• A flow-through cell
• A water bath that maintains the temperature of dissolution medium at 37±0.5°C
• Specified cell size used as mentioned in the monograph
• Pump forces dissolution medium upwards
• Pump: Delivery range between 240-960 ml per hour; Standard flow rates of 4, 8 and 16 ml per minute and must
deliver a constant flow; Kept separated from dissolution unit to shield from vibrations
• Flow profile is sinusoidal with a pulsation of 120±10 pulses per minute
• Dissolution procedures is characterized according to rate and pulsation
• Flow through cell:
• Made up of inert and transparent material
• Mounted vertically with filter system that prevents escape of undissolved particles from top of cell
• Standard cell diameters: 12 and 22.6 mm
• Bottom cone is usually filled with small glass beads of 1 mm diameter with one bead of about 5 mm
positioned at apex to protect fluid entry tube
• A tablet holder for positioning special dosage forms
• Immersed in water bath maintained at temperature 37±0.5°C
• Cell is assembled with clamp and two O-rings
• Tube connections are as short as possible and inert such as polytef with about 1.6 mm inner diameter and
chemically inert 35
Fig. 14 USP Apparatus 4 Flow Through Cell Fig. 14 USP Apparatus 4 Flow Through Cell
(a) Small cells for tablets and capsules (b) Large cells for tablets and capsules 36
Table-9 Apparatus Used for Different Dosage Forms
Apparatus Name Dosage Forms
Apparatus 1 Rotating basket Tablets
Tablets, capsules, modified drug products,

Apparatus 2 Paddle
suspensions
Apparatus 3 Reciprocating cylinder Extended-release drug products
Apparatus 4 Flow through cell Drug products containing low-water-soluble drugs
37
Table-10
• For immediate and extended-release solid dosage form: Number
tested
S1 6
37±0.5°C Q*+5%
• Introduce capsule directly into apparatus and operate at Average of 12 units
(S1+S2) is equal to or
specified rate S2 6
greater than Q, and no unit
• Withdraw specimen at specified time period (±2%) from not is less than Q-15%
less than 1 cm from vessel wall Average of 24 units

(S1+S2+S3) is equal to or
• The requirements are met if the quantity of the active greater than Q, not more
S3 12
than 2 units are less than
ingredient dissolved relies to table-10 and table-11
Q-15% and no unit is less
• For conventional dosage form, if results does not relies at than Q-25%**
stage S1, carry out stage S2 and S3 *Q is the specified amount of dissolved active substance, expressed as
the % of the labelled content;
5%, 15% and 25% are the percentages of labelled content
38
UNITED STATESPHARMACOPOEIA DISSOLUTION TEST
• For extended-release dosage form, if results does not relies at stage L1, carry out stage L2 and L3 until it conform
with L2
Table-11
L1 6
L3 12 the 24 units are more than 10% of the labelled content below the
20% of labelled content outside each of the stated ranges or more
than 20% of labelled content below the stated amount at the final test
39
time.
• For delayed release solid dosage form: Two methods are used; Method A or Method B
Table-12
Method A Method B
• Acid stage
• Acid stage
• 1000 ml of 0.1N Hydrochloric acid
• 750 ml of 0.1N Hydrochloric acid
• Warm to 37±0.5°C
• Warm to 37±0.5°C
• Place one dosage unit and operate at specified rate for 2
hours
hours
• Buffer stage
• Buffer stage
• 1000 ml of pH 6.8 phosphate buffer (3 volumes of 0.1 N
hydrochloric acid and 1 volume 0.2 M tribasic sodium
• Add 250 ml of 0.2 M solution of tribasic sodium
phosphate) warmed at 37±0.5°C
phosphate warmed at 37±0.5°C
• Adjust pH to 6.8±0.05 with 2 N hydrochloric acid or 2 N
• Adjust pH to 6.8±0.05 with 2 N hydrochloric acid or 2 N
sodium hydroxide
sodium hydroxide
40
Table-13
Table-14
Number
tested Level Acceptance criteria
tested
No individual value exceeds 10%
A1 6
dissolved B1 6 Each unit is not less than Q+5%
A2 6 B2 6 equal to or greater than Q, and no
unit is less than Q-15%
25% dissolved

is not more than 10% dissolved is equal to or greater than Q, not
A3 12 B3 12 more than 2 units are less than Q-
than 25% dissolved 15% and no unit is less than Q-
25% 41
2. Apparatus 3:
• For immediate and extended-release dosage form:
• Place the dissolution medium and maintain temperature at 37±0.5°C
• Introduce one dosage form unit directly into each of the six reciprocating cylinders
• For delayed release dosage form:
• Same as Method B described in Apparatus 1 and Apparatus 2 for acid stage
• Follow one row of vessels
• Change the volume of medium in buffer stage to 300 ml
42
3. Apparatus 4:
• For immediate and extended release dosage form:
• Place one dosage unit at the top of the bead
• Allow dissolution medium by pump through bottom of cell, warmed at 37±0.5°C
• Repeat test with additional dosage unit
• For delayed release dosage form:
• Same as described in Apparatus 1 and Apparatus 2 using specified media
43
BRITISH PHARMACOPOEIA
Uniformity
of dosage Dissolution
units test
Uniformity Disintegration
of mass test
Content of
Uniformity
active
of content
ingredient
44
BRITISH PHARMACOPOEIA UNIFORMITY OF DOSAGE UNIT
• Uniformity of dosage unit is divided into two parts:

• Test for content uniformity
• Test for mass variation

• Test for content uniformity:
• Test is carried out to check whether individual components are within the limit
• Can be applied in all cases
• 10 units are assayed individually by appropriate analytical method
• Acceptance value is calculated by formula;
Acceptance value=
where M= reference value,
= mean of individual components expressed as percentage of label claim,
k=acceptability constant and
s=sample standard deviation
45
BRITISH PHARMACOPOEIA UNIFORMITY OF DOSAGE UNIT
• Test for mass variation:
• Calculate the acceptance value and consider concentration is uniform
• For hard capsules,
• 10 capsules weighed individually and shells are removed
• Empty the contents completely
• Weigh the empty shell and the contents
• Calculate the weight of active substance and mass of product removed from each capsule
• Acceptance value is calculated by assay method
• For soft capsules,
• 10 capsules weighed individually
• Shell is cut and removed using suitable solvent
• Dried for 30 minutes at room temperature for evaporation of solvent
• Weigh the empty shell and the contents
• Calculate the weight of active substance and mass of product removed from each capsule
46
• Acceptance value is calculated by assay method
BRITISH PHARMACOPOEIA UNIFORMITY OF WEIGHT (MASS)
• Weigh individually 20 capsules

• Open the capsule and remove the contents completely
• For soft capsules, remove shell carefully by washing with suitable solvent and dried at room temperature
• Weigh the shell
• Difference in mass of contents is calculated
• Not more 2 capsules should deviate from the average mass by more than the percentage deviation in table-15
Table-15
Average mass
of Percentage deviation
capsule contents
Less than 300 mg 10
300 mg or more 7.5

47
BRITISH PHARMACOPOEIA UNIFORMITY OF CONTENT
• Based on the assay of the individual contents

• 10 units are taken and individual contents are determined using suitable analytical method
• Test B of the monograph is carried out for capsules
• Test B:
Take 10 capsules and determine individual contents by analytical method
If not more than one contents obtained is outside the If more than three individual contents are
limits 85-115% of average content Fails outside the limits 85-115% and if one or
And more of the individual contents are outside
None is outside the limits 75-125% of average content the limits 75-125% of the average value
Passes
If in all 30 capsules, not more than three
individual contents are outside the limits
Repeat using
Test passes 85-115% and none of the individual
another 20 capsules
content are outside the limits 75-125% of
the average content
48
BRITISH PHARMACOPOEIA CONTENT OF ACTIVE INGREDIENT
• Range for content of active ingredient is stated in monograph

• Test is carried out by assay
• Range is based on 20 capsules or such numbers as indicated in monograph
• Less than 5 capsules cannot be used
• Limits are between 90 and 110 percent for requirements of table-16
• Deviation from this limits needs smaller or larger allowances
Table-16
Subtract from the lower limit for Add to the upper limit for the
Weight of active ingredients in each the samples of samples of
Capsules
15 10 5 15 10 5
0.12 g or less 0.2 0.7 1.6 0.3 0.8 1.8
More than 0.12 g and less than 0.3 g 0.2 0.5 1.2 0.3 0.6 1.5
0.3 g or more 0.1 0.2 0.8 0.2 0.4 1.0

49
BRITISH PHARMACOPOEIA DISINTEGRATION TEST
• Determines whether dosage form disintegrate in prescribed time and liquid medium under prescribed experimental
conditions
• Two Basket-rack assembly apparatus are used:
• Apparatus A: capsules of not more than 18 mm long
• Apparatus B: capsules of more than 18 mm long
• Apparatus A specifications: Consist of six cylindrical glass tubes (77.5±2.5 mm long, 21.85±1.15 mm internal diameter and
1.9±0.9 mm wall thickness), Medium is at 37±2°C
• Apparatus B specifications: Consist of three cylindrical glass tubes (77.5±2.5 mm long, 33±0.5 mm internal diameter and
2.5±0.5 mm wall thickness), Medium is at 35-39°C
• Operation time (if not specified): Hard gelatin capsules (30 mins) and Soft gelatin capsules (30 mins)
• Method:
• Introduce one capsule in each glass tube
• Suspend the beaker into the specified medium for specified time
50
BRITISH PHARMACOPOEIA DISINTEGRATION TEST
• Test passes if all six capsules disintegrate
• If one or two capsules does not disintegrate completely,
• Repeat taking another 12 capsules
• Passes if 16 of the total 18 capsules disintegrate
• Gastro-resistant capsules:
• Operated for 2 hours taking 0.1 M hydrochloric acid as the medium
• No disintegration should take place
• Replace the medium with mixed phosphate buffer pH 6.8 with added pancreas powder
• Operated for 60 minutes
• If capsule fails, results are invalid
51
BRITISH PHARMACOPOEIA DISSOLUTION TEST
• Test for determining the compliance of solid dosage form with the dissolution requirements
52
Table-17
• For conventional and prolonged-release solid dosage form: Number
tested
S1 6
37±0.5°C Q*+5%
• Introduce capsule directly into apparatus and operate at Average of 12 units
(S1+S2) is equal to or
specified rate S2 6
greater than Q, and no unit
• Withdraw specimen at specified time period (±2%) from not is less than Q-15%
less than 1 cm from vessel wall Average of 24 units

(S1+S2+S3) is equal to or
• The requirements are met if the quantity of the active greater than Q, not more
S3 12
than 2 units are less than
ingredient dissolved relies to table-18 and table-18
Q-15% and no unit is less
• For conventional dosage form, if results does not relies at than Q-25%**
stage S1, carry out stage S2 and S3 *Q is the specified amount of dissolved active substance, expressed as
the % of the labelled content;
5%, 15% and 25% are the percentages of labelled content
53
• For prolonged release dosage form, if results does not relies at stage L1, carry out stage L2 and L3 until it conform
with L2
Table-18
L1 6
L3 12
the 24 units are more than 10% of the labelled content below the
20% of labelled content outside each of the stated ranges or more than
20% of labelled content below the stated amount at the final test54 time.
• For delayed release solid dosage form: Two methods are used; Method A or Method B
Table-19
Method A Method B
• Acid stage
• Acid stage
• Warm to 37±0.5°C
• Warm to 37±0.5°C
hours
hours
• Buffer stage
• Buffer stage
• 1000 ml of pH 6.8 phosphate buffer (3 volumes of 0.1 M
hydrochloric acid and 1 volume 0.2 M trisodium
• Add 250 ml of 0.2 M solution of trisodium phosphate
phosphate dodecahydrate) warmed at 37±0.5°C
dodecahydrate warmed at 37±0.5°C
sodium hydroxide
sodium hydroxide
55
Table-20
Table-21
Number
tested Level Acceptance criteria
tested
No individual value exceeds 10%
A1 6
dissolved B1 6 No unit is not less than Q+5%
A2 6 B2 6 equal to or greater than Q, and no
unit is less than Q-15%
25% dissolved

is not more than 10% dissolved is equal to or greater than Q, not
A3 12 B3 12 more than 2 units are less than Q-
than 25% dissolved 15% and no unit is less than Q-
25% 56
2. Apparatus 3:
• Place the dissolution medium and maintain temperature at 37±0.5°C
• Introduce capsule directly into each of the six reciprocating cylinders
3. Apparatus 4:
• Place one dosage unit at the top of the bead
• Allow dissolution medium by pump through bottom of cell, warmed at 37±0.5°C
• Repeat test with additional dosage unit 57
tHANK YOU
58

In-Process AND Finished Products Quality Control Tests of Capsules

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A REPORT ON

LOVELY PROFESSIONAL UNIVERSITY, PHAGWARA, PUNJAB, INDIA

• A solid dosage form containing drug or mixture of drugs

• A solid preparation containing single dose of active substance(s)

HARD GELATIN CAPSULES SOFT GELATIN CAPSULES

0.12 g or less 0.2 0.7 1.5 0.3 0.8 1.8

0.3 g or more 0.1 0.2 0.8 0.2 0.4 1.0

Randomly take 10 capsules and determine active ingredient content

If not more than one values obtained is outside the limits

• Determines whether dosage form disintegrate in prescribed time and

• An in-vitro test for determining the release profile of

Fig. 5 Apparatus 3 Fig. 6 Apparatus

Average of 24 units (A1+A2+A3) Average of 24 units (B1+B2+B3)

Place 1 dosage unit in each tube and add a

Fill with water or specific medium as the immersion fluid

Maintain the temperature at 37±2°C and operate the apparatus

Observe the capsules for the time specified in

Capsules have disintegrated except the capsule shells

Repeat tests for 12 additional Not fewer than 16 of the total

• Test for determining the compliance of solid dosage form with

Fig. 9 Apparatus 3 Fig. 10 Apparatus

Fig. 13 USP Apparatus 3

Table-9 Apparatus Used for Different Dosage Forms

Apparatus Name Dosage Forms

Apparatus 1 Rotating basket Tablets

Tablets, capsules, modified drug products,

Apparatus 3 Reciprocating cylinder Extended-release drug products

Apparatus 4 Flow through cell Drug products containing low-water-soluble drugs

less than 1 cm from vessel wall Average of 24 units

Average of 24 units (A1+A2+A3) Average of 24 units (B1+B2+B3)

• Uniformity of dosage unit is divided into two parts:

• Weigh individually 20 capsules

Less than 300 mg 10

300 mg or more 7.5

• Based on the assay of the individual contents

• Range for content of active ingredient is stated in monograph

0.12 g or less 0.2 0.7 1.6 0.3 0.8 1.8

0.3 g or more 0.1 0.2 0.8 0.2 0.4 1.0

less than 1 cm from vessel wall Average of 24 units

Average of 24 units (A1+A2+A3) Average of 24 units (B1+B2+B3)

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