Quality control test of for tablet
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May 11, 2019
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About This Presentation
Quality control test of for tablet
Slide Content
TABLETS
G
GALGOTIAS
UNIVERSITY
G
GALGOTIAS
UNIVERSITY
zo
Quality control test for Tablets
e Whether tablets are produced on a small scale or large scale
all of them are required to pass through certain tests i.e.,
quality control tests to test the quality of the finished product.
e Following quality control test can be performed for tablets:
I. Weight variation test VI. Disintegration test
II. Content of active ingredients VII. Dissolution test
IH. Uniformity of content VILL. Contents of Packaged Dosage
IV. Hardness of tablets Forms
V. Friability of Uncoated Tablets IX. Content labelling requirement
Quality control test for Tablets
e Whether tablets are produced on a small scale or large scale
all of them are required to pass through certain tests i.e.,
quality control tests to test the quality of the finished product.
e Following quality control test can be performed for tablets:
I. Weight variation test VI. Disintegration test
II. Content of active ingredients VII. Dissolution test
IH. Uniformity of content VILL. Contents of Packaged Dosage
IV. Hardness of tablets Forms
V. Friability of Uncoated Tablets IX. Content labelling requirement
(4. Weight variation test (Official):
e This test 1s based on the fact that, if the weight variation is
not much then it can be said that the amount of medicament
will not vary considerably.
© Conversely, if the weight variation is larger then it can be
concluded that the active medicament will also vary
considerably.
Sources of weight variation
e Weight variation is solely dependent on the poor flow
property of granules and filling of die cavity.
e Poor flow properties arise from:
1. Improper lubrication
u. Size of granules
tii. Adjustment of lower punch.
e This test 1s based on the fact that, if the weight variation is
not much then it can be said that the amount of medicament
will not vary considerably.
© Conversely, if the weight variation is larger then it can be
concluded that the active medicament will also vary
considerably.
Sources of weight variation
e Weight variation is solely dependent on the poor flow
property of granules and filling of die cavity.
e Poor flow properties arise from:
1. Improper lubrication
u. Size of granules
tii. Adjustment of lower punch.
Po
Weigh individually 20 units selected at random or, for single dose
preparations in individual containers, the contents of 20 units, and
calculate the average weight.
e 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.
e This test is not applicable to coated tablets other than film-coated
tablets and to tablets that are required to comply with the test for
uniformity of content for all active ingredients.
Dosage form Average weight Percentage
deviation
Uncoated and film- 80 mg or less 10
coated tablets
More than 80 mg but TS
less than 250 mg
n
250 mg or more
Weigh individually 20 units selected at random or, for single dose
preparations in individual containers, the contents of 20 units, and
calculate the average weight.
e 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.
e This test is not applicable to coated tablets other than film-coated
tablets and to tablets that are required to comply with the test for
uniformity of content for all active ingredients.
Dosage form Average weight Percentage
deviation
Uncoated and film- 80 mg or less 10
coated tablets
More than 80 mg but TS
less than 250 mg
n
250 mg or more
II. Content of active ingredients:
e Determine the amount of active ingredient(s) by the method
described in the Assay and calculate the amount of active
ingredient(s) per tablet.
e The result lies within the range for the content of active
ingredient(s) stated in the monograph.
e This range is based on the requirement that 20 tablets, or
such other number as may be indicated in the monograph, are
used in the Assay.
e Where 20 tablets cannot be obtained, a smaller number,
which must not be less than 5, may be used, but to allow for
sampling errors the tolerances are widened in accordance
with Table.
e Determine the amount of active ingredient(s) by the method
described in the Assay and calculate the amount of active
ingredient(s) per tablet.
e The result lies within the range for the content of active
ingredient(s) stated in the monograph.
e This range is based on the requirement that 20 tablets, or
such other number as may be indicated in the monograph, are
used in the Assay.
e Where 20 tablets cannot be obtained, a smaller number,
which must not be less than 5, may be used, but to allow for
sampling errors the tolerances are widened in accordance
with Table.
a
e The requirements of Table apply when the stated limits are
between 90 and 110 per cent.
e For limits other than 90 to 110 percent, proportionately
smaller or larger allowances should be made.
Table 1
Weight of active Subtract from Add to the upper
ingredients in each lower limit limit for
tablet for samples of samples of
15 10 3 15 10 5
0.12 gor less 02 07 16 03 08 18
More than 0.12 g 02 #05 12 05 06 15
but less than 0.3 g
0.3 gor more 01 02 08 02 04 10
e The requirements of Table apply when the stated limits are
between 90 and 110 per cent.
e For limits other than 90 to 110 percent, proportionately
smaller or larger allowances should be made.
Table 1
Weight of active Subtract from Add to the upper
ingredients in each lower limit limit for
tablet for samples of samples of
15 10 3 15 10 5
0.12 gor less 02 07 16 03 08 18
More than 0.12 g 02 #05 12 05 06 15
but less than 0.3 g
0.3 gor more 01 02 08 02 04 10
17
IH. Uniformity of content:
The test for uniformity of content of single-dose
preparations 1s based on the assay of the individual contents
of active substance 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.
This test is applicable to tablets that contain 10 mg or less
than 10 mg or less than 10 per cent w/w of active ingredient.
For tablets containing more than one active ingredient carry
out the test for each active ingredient that corresponds to the
aforementioned conditions.
The test is also applicable to coated tablets other than film
coated tablets, irrespective of their content of active
substance(s).
IH. Uniformity of content:
The test for uniformity of content of single-dose
preparations 1s based on the assay of the individual contents
of active substance 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.
This test is applicable to tablets that contain 10 mg or less
than 10 mg or less than 10 per cent w/w of active ingredient.
For tablets containing more than one active ingredient carry
out the test for each active ingredient that corresponds to the
aforementioned conditions.
The test is also applicable to coated tablets other than film
coated tablets, irrespective of their content of active
substance(s).
Gr
e The test for Uniformity of content should be carried out
only after the content of active ingredient(s) in a pooled
sample of the tablets has been shown to be within accepted
limits of the stated content.
e Note: - The test for Uniformity of content is not applicable
to tablets containing multivitamins and trace elements.
Method:
e 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
e The preparation complies with the test if each individual
content is 85 to 115 per cent of the average content.
e The test for Uniformity of content should be carried out
only after the content of active ingredient(s) in a pooled
sample of the tablets has been shown to be within accepted
limits of the stated content.
e Note: - The test for Uniformity of content is not applicable
to tablets containing multivitamins and trace elements.
Method:
e 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
e The preparation complies with the test if each individual
content is 85 to 115 per cent of the average content.
The preparation fails to comply with the test if more than
one individual content is outside these limits or if one
individual content is outside the limits of 75 to 125 per cent
of the average content.
If one individual content is 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 one
of the individual contents of the total sample of 30 dosage
units is outside 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.
one individual content is outside these limits or if one
individual content is outside the limits of 75 to 125 per cent
of the average content.
If one individual content is 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 one
of the individual contents of the total sample of 30 dosage
units is outside 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.
a
e NOTE - The test is not applicable for capsules containing
multivitamins and trace elements.
Determine the content of active ingredient in each of 10 capsules
taken at random using the method given in the monograph or by any
other suitable analytical method of equivalent accuracy and precision.
The capsules comply with the test if not more than one of the
individual values thus obtained is outside the limits 85 to 115 per cent
of the average value and none is outside the limits 75 to 125 per cent.
If two or three individual values are outside the limits 85 to 115
percent of the average value repeat the determination using another
20 capsules.
The capsules comply with the test if in the total sample of 30
capsules not more than three individual values are outside the limits
85 to 115 per cent and none is outside the limits 75 to 125 per cent of
the average value.
e NOTE - The test is not applicable for capsules containing
multivitamins and trace elements.
Determine the content of active ingredient in each of 10 capsules
taken at random using the method given in the monograph or by any
other suitable analytical method of equivalent accuracy and precision.
The capsules comply with the test if not more than one of the
individual values thus obtained is outside the limits 85 to 115 per cent
of the average value and none is outside the limits 75 to 125 per cent.
If two or three individual values are outside the limits 85 to 115
percent of the average value repeat the determination using another
20 capsules.
The capsules comply with the test if in the total sample of 30
capsules not more than three individual values are outside the limits
85 to 115 per cent and none is outside the limits 75 to 125 per cent of
the average value.
Ow. Hardness of tablets:
e The resistance of the tablet to chipping, abrasion or breakage
under conditions of storage, transportation and handling before
usage depends on its hardness.
Method:
e A tablet is taken between the 2nd and 3rd finger and pressing it
with the thumb as fulcrum. If the tablet breaks with a “sharp snap”.
yet, it does not break when it falls on the floor — is said to possess
proper hardness.
Instruments used:
i Monsanto Hardness Tester
Manual mode of
ii. Strong Cobb Hardness Tester operation are more
wes or less similar
iii. Pfizer Hardness Tester .
. , . Operates without
iv. Schleuniger Apparatus aaa eas
o manual involvement.
e The resistance of the tablet to chipping, abrasion or breakage
under conditions of storage, transportation and handling before
usage depends on its hardness.
Method:
e A tablet is taken between the 2nd and 3rd finger and pressing it
with the thumb as fulcrum. If the tablet breaks with a “sharp snap”.
yet, it does not break when it falls on the floor — is said to possess
proper hardness.
Instruments used:
i Monsanto Hardness Tester
Manual mode of
ii. Strong Cobb Hardness Tester operation are more
wes or less similar
iii. Pfizer Hardness Tester .
. , . Operates without
iv. Schleuniger Apparatus aaa eas
o manual involvement.
e The hardness at which the tablet crushes is the hardness of
the tablet.
Unit of hardness: - Kg/sq.in. or Ib/ sq.in
e Limit : Generally maximum 5 kg/sq.in. hardness is
required.
Note: -
e If the tablets are too hard then it may not meet tablet
disintegration test.
e If the tablets are too soft then it may not with stand the
handling, packaging and shipping operations.
the tablet.
Unit of hardness: - Kg/sq.in. or Ib/ sq.in
e Limit : Generally maximum 5 kg/sq.in. hardness is
required.
Note: -
e If the tablets are too hard then it may not meet tablet
disintegration test.
e If the tablets are too soft then it may not with stand the
handling, packaging and shipping operations.
(x. Friability of Uncoated Tablets:
e This test is applicable to compressed tablets and is intended to
determine the physical strength of tablets.
Apparatus:
e It consists of a drum of transparent synthetic polymer with
polished internal surfaces and subject to minimum static build-up.
e It has a diameter of 283-291 mm and a depth of 36-40 mm (see
figure); one side of the drum is removable.
e A curved projection with an inner radius of 75.5 mm to 85.5 mm
and extending from the middle of the drum to the outer wall
enables the tumbling of the tablets at each turn of the drum.
e The outer diameter of the central ring is 24.5 mm to 25.5 mm.
e The drum is attached to the horizontal axis of a device that
rotates at 25 + 1 rpm.
e = It should be ensured that with every turn of the drum the tablets
roll or slide and fall onto the drum wall or onto each other.
e This test is applicable to compressed tablets and is intended to
determine the physical strength of tablets.
Apparatus:
e It consists of a drum of transparent synthetic polymer with
polished internal surfaces and subject to minimum static build-up.
e It has a diameter of 283-291 mm and a depth of 36-40 mm (see
figure); one side of the drum is removable.
e A curved projection with an inner radius of 75.5 mm to 85.5 mm
and extending from the middle of the drum to the outer wall
enables the tumbling of the tablets at each turn of the drum.
e The outer diameter of the central ring is 24.5 mm to 25.5 mm.
e The drum is attached to the horizontal axis of a device that
rotates at 25 + 1 rpm.
e = It should be ensured that with every turn of the drum the tablets
roll or slide and fall onto the drum wall or onto each other.
Fig.: Tablet friability apparatus
( Method:
e For tablets with an average weight of 0.65 g or less take a
sample of whole tablets corresponding to about 6.5 g.
For tablets with an average weight of more than 0.65 g take
asample of 10 whole tablets.
e Dedust the tablets carefully and weigh accurately the
required number of tablets.
e Place the tablets in the drum and rotate it 100 times.
Remove the tablets, remove any loose dust from them and
weigh them accurately.
e The test is run only once unless the results are difficult to
interpret or if the weight loss is greater than the targeted
value, in which case, the test is repeated twice and the mean
of the three tests is determined.
e For tablets with an average weight of 0.65 g or less take a
sample of whole tablets corresponding to about 6.5 g.
For tablets with an average weight of more than 0.65 g take
asample of 10 whole tablets.
e Dedust the tablets carefully and weigh accurately the
required number of tablets.
e Place the tablets in the drum and rotate it 100 times.
Remove the tablets, remove any loose dust from them and
weigh them accurately.
e The test is run only once unless the results are difficult to
interpret or if the weight loss is greater than the targeted
value, in which case, the test is repeated twice and the mean
of the three tests is determined.
A maximum loss of weight (from a single test or from the
mean of the three tests) not greater than 1.0 per cent is
acceptable for most tablets.
If obviously cracked, chipped or broken tablets are
present in the sample after tumbling, the sample fails the
test.
If the size or shape of the tablet causes irregular tumbling,
adjust the drum base so that it forms an angle of about 10°
with the horizontal and the tablets do not bind together
when lying next to each other, which prevents them from
falling Freely.
mean of the three tests) not greater than 1.0 per cent is
acceptable for most tablets.
If obviously cracked, chipped or broken tablets are
present in the sample after tumbling, the sample fails the
test.
If the size or shape of the tablet causes irregular tumbling,
adjust the drum base so that it forms an angle of about 10°
with the horizontal and the tablets do not bind together
when lying next to each other, which prevents them from
falling Freely.
(x
e This test determines whether dosage forms such as tablets,
JL Disintegration test:
capsules disintegrate within a prescribed time when placed in a
liquid medium under the prescribed experimental conditions.
e For the purpose of this test, disintegration does not imply
complete solution of the dosage unit or even of its active
constituent.
e Disintegration is defined as that state in which no residue of the
unit under test remains on the screen of the apparatus.
e Ifa residue remains, it consists of fragments of disintegrated
parts of tablets component, parts such as insoluble coating of
the tablets.
e If discs have been used with tablets, any residue remaining on
the lower surfaces of the discs consists only of fragments of
shells.
e This test determines whether dosage forms such as tablets,
JL Disintegration test:
capsules disintegrate within a prescribed time when placed in a
liquid medium under the prescribed experimental conditions.
e For the purpose of this test, disintegration does not imply
complete solution of the dosage unit or even of its active
constituent.
e Disintegration is defined as that state in which no residue of the
unit under test remains on the screen of the apparatus.
e Ifa residue remains, it consists of fragments of disintegrated
parts of tablets component, parts such as insoluble coating of
the tablets.
e If discs have been used with tablets, any residue remaining on
the lower surfaces of the discs consists only of fragments of
shells.
Disintegration test method for tablets and capsules:
e Apparatus
i. The apparatus consists of a basket-rack assembly,
ii. Al-litre beaker,
iii. Athermostatic arrangement for heating the fluid and
iv. A mechanical device for raising and lowering the basket in the
immersion fluid at a constant frequency rate.
i. Basket-rack assembly
e The basket-rack assembly is rigid and supports six cylindrical
glass tubes, 77.5 + 2.5 mm long, 21.5 mm in internal diameter
and with a wall thickness of about 2 mm (as shown in Figure).
e The tubes are held vertically by two superimposed transparent
plastic plates, 90 + 2 mm in diameter and 6.75 + 1.75 mm thick
perforated by six holes having the same diameter as the tubes.
e Apparatus
i. The apparatus consists of a basket-rack assembly,
ii. Al-litre beaker,
iii. Athermostatic arrangement for heating the fluid and
iv. A mechanical device for raising and lowering the basket in the
immersion fluid at a constant frequency rate.
i. Basket-rack assembly
e The basket-rack assembly is rigid and supports six cylindrical
glass tubes, 77.5 + 2.5 mm long, 21.5 mm in internal diameter
and with a wall thickness of about 2 mm (as shown in Figure).
e The tubes are held vertically by two superimposed transparent
plastic plates, 90 + 2 mm in diameter and 6.75 + 1.75 mm thick
perforated by six holes having the same diameter as the tubes.
at
The holes are equidistant from the centre of the plate and are
equally spaced from one another.
The tubes are attached to the under side of the lower plate, is a
woven stainless steel wire cloth with a plain square weave with 2.0
+ 0.2 mm mesh apertures and with a wire diameter of 0.615 +
0.045 mm.
The upper plate is covered with a stainless steel disc perforated
by six holes, each about 24 + 2 mm in diameter, which fits over the
tubes and holds them between the plastic plates.
The holes coincide with those of the upper plastic plate and the
upper open ends of the glass tubes.
A suitable means is provided to suspend the basket-rack
assembly from the raising and lowering device using a point on its
AXIS.
The holes are equidistant from the centre of the plate and are
equally spaced from one another.
The tubes are attached to the under side of the lower plate, is a
woven stainless steel wire cloth with a plain square weave with 2.0
+ 0.2 mm mesh apertures and with a wire diameter of 0.615 +
0.045 mm.
The upper plate is covered with a stainless steel disc perforated
by six holes, each about 24 + 2 mm in diameter, which fits over the
tubes and holds them between the plastic plates.
The holes coincide with those of the upper plastic plate and the
upper open ends of the glass tubes.
A suitable means is provided to suspend the basket-rack
assembly from the raising and lowering device using a point on its
AXIS.
Fa
e The plates are held rigidly in position and 77.5 mm apart by
vertical metal rods at the periphery and a metal rod is also fixed to
the centre of the upper plate to enable the assembly to be attached
to the device for raising and lowering it smoothly at a constant
frequency of between 28 and 32 cycles per minute through a
distance of 50 to 60 mm.
e The time required for the upward stroke is equal to the time
required for the downward stroke, and the change in stroke
direction should be smooth and not abrupt.
e = There should be no appreciable horizontal motion or movement
of the axis from the vertical.
e The design of the basket-rack assembly may be somewhat
different provided specifications for the glass tubes and the screen
mesh size are unchanged.
e The plates are held rigidly in position and 77.5 mm apart by
vertical metal rods at the periphery and a metal rod is also fixed to
the centre of the upper plate to enable the assembly to be attached
to the device for raising and lowering it smoothly at a constant
frequency of between 28 and 32 cycles per minute through a
distance of 50 to 60 mm.
e The time required for the upward stroke is equal to the time
required for the downward stroke, and the change in stroke
direction should be smooth and not abrupt.
e = There should be no appreciable horizontal motion or movement
of the axis from the vertical.
e The design of the basket-rack assembly may be somewhat
different provided specifications for the glass tubes and the screen
mesh size are unchanged.
Discs
A cylindrical disc for each tube, each 20.7 + 0.15 mm thick
in diameter and 9.5 + 0.15 mm thick, made of transparent
plastic with a relative density of 1.18 to 1.20, and pierced
with five holes, each 2 mm in diameter, one in the centre and
the other four spaced equally on a circle of radius 6 mm from
the centre of the disc.
Four equally-spaced grooves are cut in the lateral surface of
the disc in such a way that at the upper surface of the disc
they are 9.5 mm wide and 2.55 mm deep and at the lower
surface 1.6 mm square.
A cylindrical disc for each tube, each 20.7 + 0.15 mm thick
in diameter and 9.5 + 0.15 mm thick, made of transparent
plastic with a relative density of 1.18 to 1.20, and pierced
with five holes, each 2 mm in diameter, one in the centre and
the other four spaced equally on a circle of radius 6 mm from
the centre of the disc.
Four equally-spaced grooves are cut in the lateral surface of
the disc in such a way that at the upper surface of the disc
they are 9.5 mm wide and 2.55 mm deep and at the lower
surface 1.6 mm square.
Medium
e The assembly is suspended in the liquid medium in a
suitable vessel, preferably a 1-litre beaker.
e The volume of liquid is such that the wire mesh at its
highest point is at least 25 mm below the surface of the
liquid, and at its lower point is at least 25 mm above the
bottom of the beaker.
e At no time should the top of the basket-rack assembly
become submerged.
e There is a thermostatic arrangement for heating the liquid
and maintaining the temperature at 37° + 2°.
e The assembly is suspended in the liquid medium in a
suitable vessel, preferably a 1-litre beaker.
e The volume of liquid is such that the wire mesh at its
highest point is at least 25 mm below the surface of the
liquid, and at its lower point is at least 25 mm above the
bottom of the beaker.
e At no time should the top of the basket-rack assembly
become submerged.
e There is a thermostatic arrangement for heating the liquid
and maintaining the temperature at 37° + 2°.
(Dimensions in mm)
Apparatus for Disintegration of Tablets and Capsules
Apparatus for Disintegration of Tablets and Capsules
Disintegration test apparatus Top view of Disintegration
process of capsules
process of capsules
( Method
e Unless otherwise stated in the individual monograph,
introduce one tablet or capsule into each tube and, if directed
in the appropriate general monograph, add a disc to each
tube.
e Suspend the assembly in the beaker containing the specified
liquid and operate the apparatus for the specified time.
e Remove the assembly from the liquid.
e The tablets pass the test if all of them have disintegrated.
e If 1 or 2 tablets fail to disintegrate. Repeat the test on 12
additional tablets; not less than 16 of the total of 18 tablets
tested disintegrate.
e Unless otherwise stated in the individual monograph,
introduce one tablet or capsule into each tube and, if directed
in the appropriate general monograph, add a disc to each
tube.
e Suspend the assembly in the beaker containing the specified
liquid and operate the apparatus for the specified time.
e Remove the assembly from the liquid.
e The tablets pass the test if all of them have disintegrated.
e If 1 or 2 tablets fail to disintegrate. Repeat the test on 12
additional tablets; not less than 16 of the total of 18 tablets
tested disintegrate.
at
If the tablets 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 tablets in the
repeat test disintegrate.
Where required, the requirements for this test are given in the
individual monographs.
Where a dissolution test is prescribed, the disintegration test may
not be necessary.
Note: - The test does not apply to chewable tablets.
Uncoated Tablets
Uncoated tablets may be single-layer tablets resulting from a
single compression of particles or multi-layer tablets consisting of
parallel layers obtained by successive compression of particles of
different compositions.
If the tablets 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 tablets in the
repeat test disintegrate.
Where required, the requirements for this test are given in the
individual monographs.
Where a dissolution test is prescribed, the disintegration test may
not be necessary.
Note: - The test does not apply to chewable tablets.
Uncoated Tablets
Uncoated tablets may be single-layer tablets resulting from a
single compression of particles or multi-layer tablets consisting of
parallel layers obtained by successive compression of particles of
different compositions.
No treatment is applied to such tablets after compression.
Any added substances are not specifically intended to
modify the release of their active ingredient(s) in the
digestive fluids.
The addition of flavouring agents to uncoated tablets other
than multi-layer tablets is not official unless permitted in the
individual monograph.
Uncoated Tablets have the general characteristics of tablets.
When a broken section of an uncoated tablet is examined
under a lens, either a relatively uniform texture (single-layer
tablets) or a stratified structure (multi-layer tablets) is seen:
there are no signs of coating.
Any added substances are not specifically intended to
modify the release of their active ingredient(s) in the
digestive fluids.
The addition of flavouring agents to uncoated tablets other
than multi-layer tablets is not official unless permitted in the
individual monograph.
Uncoated Tablets have the general characteristics of tablets.
When a broken section of an uncoated tablet is examined
under a lens, either a relatively uniform texture (single-layer
tablets) or a stratified structure (multi-layer tablets) is seen:
there are no signs of coating.
OT
ests
e Disintegration: -
e Use water as the liquid.
e Add a disc to each tube.
e Operate the apparatus for 15 minutes, unless otherwise stated
in the individual monograph.
e Examine the state of the tablets.
e Tf the tablets fail to comply because of adherence to the discs,
repeat the test on a further 6 tablets omitting the discs.
e The tablets comply with the test if all 6 tablets have
disintegrated.
Coated Tablets
© Coated tablets are tablets covered with one or more layers of
mixtures of various substances such as resins, gums, inactive
and insoluble fillers, sugars, plasticisers, polyhydric alcohols,
waxes, etc.
ests
e Disintegration: -
e Use water as the liquid.
e Add a disc to each tube.
e Operate the apparatus for 15 minutes, unless otherwise stated
in the individual monograph.
e Examine the state of the tablets.
e Tf the tablets fail to comply because of adherence to the discs,
repeat the test on a further 6 tablets omitting the discs.
e The tablets comply with the test if all 6 tablets have
disintegrated.
Coated Tablets
© Coated tablets are tablets covered with one or more layers of
mixtures of various substances such as resins, gums, inactive
and insoluble fillers, sugars, plasticisers, polyhydric alcohols,
waxes, etc.
e «|
The coating may also contain medicaments.
In compression-coated tablets, the coating is applied by
compressing around the tablets granules prepared from tablet
excipients such as lactose, calcium phosphate, etc.
Substances used as coatings are usually applied as a solution
or suspension in conditions in which evaporation of the
vehicle occurs.
When the coating is thin, the tablets are described as film-
coated.
Coated tablets may contain flavouring agents.
Coated tablets have a smooth, usually polished and often
coloured, surface: a broken section examined under a lens
shows a core surrounded by one or more continuous layers of
a different texture.
The coating may also contain medicaments.
In compression-coated tablets, the coating is applied by
compressing around the tablets granules prepared from tablet
excipients such as lactose, calcium phosphate, etc.
Substances used as coatings are usually applied as a solution
or suspension in conditions in which evaporation of the
vehicle occurs.
When the coating is thin, the tablets are described as film-
coated.
Coated tablets may contain flavouring agents.
Coated tablets have a smooth, usually polished and often
coloured, surface: a broken section examined under a lens
shows a core surrounded by one or more continuous layers of
a different texture.
Tests
e Disintegration (For coated tablets other than film coated
tablets): -
e Use water as the liquid.
e Add a disc to each tube.
e Operate the apparatus for 60 minutes, unless otherwise stated
in the individual monograph.
e Examine the state of the tablets.
e = If any of the tablets has not disintegrated, repeat the test on a
further 6 tablets, replacing water with 0.1 M hydrochloric acid.
e The tablets comply with the test if all 6 tablets have
disintegrated in the acid medium.
e Disintegration (For coated tablets other than film coated
tablets): -
e Use water as the liquid.
e Add a disc to each tube.
e Operate the apparatus for 60 minutes, unless otherwise stated
in the individual monograph.
e Examine the state of the tablets.
e = If any of the tablets has not disintegrated, repeat the test on a
further 6 tablets, replacing water with 0.1 M hydrochloric acid.
e The tablets comply with the test if all 6 tablets have
disintegrated in the acid medium.
For film-coated tablets: -
e Carry out the test described above but operate the apparatus for
30 minutes, unless otherwise stated in the individual Monograph.
e = If coated tablets fail to comply because of adherence to the discs,
repeat the test on a further 6 tablets omitting the discs.
e The tablets comply with the test if all 6 tablets have
disintegrated.
Dispersible Tablets: -
e Dispersible tablets are uncoated or film-coated tablets that
produce a uniform dispersion in water and may contain permitted
flavouring and sweetening agents.
e Carry out the test described above but operate the apparatus for
30 minutes, unless otherwise stated in the individual Monograph.
e = If coated tablets fail to comply because of adherence to the discs,
repeat the test on a further 6 tablets omitting the discs.
e The tablets comply with the test if all 6 tablets have
disintegrated.
Dispersible Tablets: -
e Dispersible tablets are uncoated or film-coated tablets that
produce a uniform dispersion in water and may contain permitted
flavouring and sweetening agents.
e However, if saccharin, including its sodium and potassium salts,
is used as a sweetening agent, its concentration in dispersible
tablets meant for paediatric use should be restricted so as to limit
its intake to 5 mg/kg of body weight.
Tes
e Disintegration: - Determine at 24° to 26° and operate the
apparatus for 3 minutes.
e Uniformity of dispersion: - Place 2 tablets in 100 ml of water
and stir gently until completely dispersed. A smooth dispersion is
obtained which passes through a sieve screen with a nominal mesh
aperture of 710 mm (sieve number 22).
is used as a sweetening agent, its concentration in dispersible
tablets meant for paediatric use should be restricted so as to limit
its intake to 5 mg/kg of body weight.
Tes
e Disintegration: - Determine at 24° to 26° and operate the
apparatus for 3 minutes.
e Uniformity of dispersion: - Place 2 tablets in 100 ml of water
and stir gently until completely dispersed. A smooth dispersion is
obtained which passes through a sieve screen with a nominal mesh
aperture of 710 mm (sieve number 22).
(E
e Effervescent tablets are uncoated tablets generally containing
ffervescent Tablets: -
acidic substances and either carbonates or bicarbonates which
react rapidly in the presence of water to release carbon dioxide.
e They are intended to be dissolved or dispersed in water before
administration.
Tests
¢ Disintegration: -
e Place one tablet in a 250-ml beaker containing water at 20° to
30°; numerous gas bubbles are evolved.
e When the evolution of gas around the tablet or it fragments has
ceased the tablet shall have disintegrated, being either
dissolved or dispersed in the water so that no agglomerates of
particles remain.
e Repeat the operation on a further 5 tablets.
e Effervescent tablets are uncoated tablets generally containing
ffervescent Tablets: -
acidic substances and either carbonates or bicarbonates which
react rapidly in the presence of water to release carbon dioxide.
e They are intended to be dissolved or dispersed in water before
administration.
Tests
¢ Disintegration: -
e Place one tablet in a 250-ml beaker containing water at 20° to
30°; numerous gas bubbles are evolved.
e When the evolution of gas around the tablet or it fragments has
ceased the tablet shall have disintegrated, being either
dissolved or dispersed in the water so that no agglomerates of
particles remain.
e Repeat the operation on a further 5 tablets.
e The tablets comply with the test if each of the 6 tablets
disintegrates in the manner prescribed within 5 minutes, unless
otherwise stated in the individual monograph.
Modified-release tablets: -
e § Modified-release tablets (Sustained-release tablets) are coated or
uncoated tablets containing auxiliary substances or prepared by
procedures that, separately or together, are designed to modify the
rate or the place at which the active ingredient is released.
e Modified-release tablets include enteric-coated tablets,
prolonged-release tablets and delayed-release tablets.
Enteric-coated Tablets
e Enteric-coated tablets (Gastro-resistant tablets) are delayed
release tablets that are intended to resist the gastric fluid but to
release their active ingredient(s) in the intestinal fluid.
disintegrates in the manner prescribed within 5 minutes, unless
otherwise stated in the individual monograph.
Modified-release tablets: -
e § Modified-release tablets (Sustained-release tablets) are coated or
uncoated tablets containing auxiliary substances or prepared by
procedures that, separately or together, are designed to modify the
rate or the place at which the active ingredient is released.
e Modified-release tablets include enteric-coated tablets,
prolonged-release tablets and delayed-release tablets.
Enteric-coated Tablets
e Enteric-coated tablets (Gastro-resistant tablets) are delayed
release tablets that are intended to resist the gastric fluid but to
release their active ingredient(s) in the intestinal fluid.
Po
For this purpose substances such as cellulose acetate phthalate
and anionic copolymers of meth-acrylic acid and its ethers are
used for providing tablets with a gastric-resistant coating or for
covering either granules or particles with gastric-resistant Coating.
e Enteric-coated tablets have the characteristics of Coated Tablets.
Tests
e Disintegration: -
e Tf the tablet has a soluble external coating, immerse the basket
in water at room temperature for 5 minutes.
e Suspend the assembly in the beaker containing 0.1 M
hydrochloric acid and operate without the discs for 120
minutes, unless otherwise stated in the individual monograph.
e Remove the assembly from the liquid.
e No tablet shows signs of cracks that would allow the escape of
the contents of disintegration, apart from fragments of coating.
For this purpose substances such as cellulose acetate phthalate
and anionic copolymers of meth-acrylic acid and its ethers are
used for providing tablets with a gastric-resistant coating or for
covering either granules or particles with gastric-resistant Coating.
e Enteric-coated tablets have the characteristics of Coated Tablets.
Tests
e Disintegration: -
e Tf the tablet has a soluble external coating, immerse the basket
in water at room temperature for 5 minutes.
e Suspend the assembly in the beaker containing 0.1 M
hydrochloric acid and operate without the discs for 120
minutes, unless otherwise stated in the individual monograph.
e Remove the assembly from the liquid.
e No tablet shows signs of cracks that would allow the escape of
the contents of disintegration, apart from fragments of coating.
e 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.
e Remove the assembly from the liquid. The tablets pass the test
if all six have disintegrated.
e Dissolution: -
e For tablets prepared from granules or particles already covered
with an enteric coating, the dissolution test is carried out to
demonstrate the appropriate release of the active substance(s).
Prolonged- release Tablets
e Prolonged-release tablets, also known as sustained-release tablets
or extended-release tablets are tablets formulated in such a manner
as to make the contained active ingredient available over an
extended period of time after ingestion.
pH 6.8, add a disc to each tube and operate the apparatus for a
further 60 minutes.
e Remove the assembly from the liquid. The tablets pass the test
if all six have disintegrated.
e Dissolution: -
e For tablets prepared from granules or particles already covered
with an enteric coating, the dissolution test is carried out to
demonstrate the appropriate release of the active substance(s).
Prolonged- release Tablets
e Prolonged-release tablets, also known as sustained-release tablets
or extended-release tablets are tablets formulated in such a manner
as to make the contained active ingredient available over an
extended period of time after ingestion.
E
ests
e Dissolution: -
e The test should be designed to demonstrate the appropriate
release of the active substance(s).
e The manufacturer is expected to give specifications for drug
release at 3 or more test-time points.
e The first point should be set after a testing period
corresponding to a dissolved amount of typically 20 per cent to
30 per cent.
e The second point should define the dissolution pattern and
should be set at around 50 per cent release.
e The final point should ensure almost complete release that is
generally understood as more than 80 per cent Release.
e Carry out the test for the test-times indicated on the label of the
product.
ests
e Dissolution: -
e The test should be designed to demonstrate the appropriate
release of the active substance(s).
e The manufacturer is expected to give specifications for drug
release at 3 or more test-time points.
e The first point should be set after a testing period
corresponding to a dissolved amount of typically 20 per cent to
30 per cent.
e The second point should define the dissolution pattern and
should be set at around 50 per cent release.
e The final point should ensure almost complete release that is
generally understood as more than 80 per cent Release.
e Carry out the test for the test-times indicated on the label of the
product.
( Soluble tablets
e Soluble tablets are uncoated tablets or film-coated tablets that are
to be dissolved in water before use.
e The solution produced may be slightly opalescent due to added
substances used in the manufacture of the tablets.
Tests
e = Disintegration: - Soluble tablets disintegrate within 3 minutes.
The test is carried out using water at 15° to 25°.
Tablets for Use in the Mouth
e Tablets for use in the mouth are usually uncoated tablets
formulated to be chewed or to effect a slow release and local
action of the active ingredient (lozenges) or the release and
absorption of the active ingredient under the tongue (sublingual
tablets).
e Chewable tablets and lozenges may contain flavouring agents.
e Soluble tablets are uncoated tablets or film-coated tablets that are
to be dissolved in water before use.
e The solution produced may be slightly opalescent due to added
substances used in the manufacture of the tablets.
Tests
e = Disintegration: - Soluble tablets disintegrate within 3 minutes.
The test is carried out using water at 15° to 25°.
Tablets for Use in the Mouth
e Tablets for use in the mouth are usually uncoated tablets
formulated to be chewed or to effect a slow release and local
action of the active ingredient (lozenges) or the release and
absorption of the active ingredient under the tongue (sublingual
tablets).
e Chewable tablets and lozenges may contain flavouring agents.
(x
‘TI. Dissolution test:
This test is designed to determine compliance with the
dissolution requirements for solid dosage forms administered
orally.
The test is intended for a capsule or tablet.
Use Apparatus 1 unless otherwise directed.
All parts of the apparatus that may come into contact with the
preparation under examination or with the dissolution medium are
chemically inert and do not adsorb, react or interfere with the
preparation under examination.
All metal parts of the apparatus that may come into contact with
the preparation or the dissolution medium must be made from
stainless steel, type 316 or equivalent or coated with a suitable
material to ensure that such parts do not react or interfere with the
preparation under examination or the dissolution medium.
‘TI. Dissolution test:
This test is designed to determine compliance with the
dissolution requirements for solid dosage forms administered
orally.
The test is intended for a capsule or tablet.
Use Apparatus 1 unless otherwise directed.
All parts of the apparatus that may come into contact with the
preparation under examination or with the dissolution medium are
chemically inert and do not adsorb, react or interfere with the
preparation under examination.
All metal parts of the apparatus that may come into contact with
the preparation or the dissolution medium must be made from
stainless steel, type 316 or equivalent or coated with a suitable
material to ensure that such parts do not react or interfere with the
preparation under examination or the dissolution medium.
o No part of the assembly, including the environment in which
the assembly is placed, contributes significant motion,
agitation or vibration beyond that due to the smoothly rotating
element.
e An apparatus that permits observation of the preparation
under examination and the stirrer during the test is preferable.
Apparatus 1
e Anassembly consisting of the following:
a. A cylindrical vessel, A, made of borosilicate glass or any other
suitable transparent material, with a hemispherical bottom and
with a nominal capacity of 1000ml and an inside diameter of
98-106 mm (Fig.2.5.2-1). The vessel has a flanged upper rim
and is fitted with a lid that has a number of openings, one of
which is central.
the assembly is placed, contributes significant motion,
agitation or vibration beyond that due to the smoothly rotating
element.
e An apparatus that permits observation of the preparation
under examination and the stirrer during the test is preferable.
Apparatus 1
e Anassembly consisting of the following:
a. A cylindrical vessel, A, made of borosilicate glass or any other
suitable transparent material, with a hemispherical bottom and
with a nominal capacity of 1000ml and an inside diameter of
98-106 mm (Fig.2.5.2-1). The vessel has a flanged upper rim
and is fitted with a lid that has a number of openings, one of
which is central.
A motor with a speed regulator capable of maintaining the
speed of rotation of the paddle within 4 per cent of that specified
in the individual monograph. The motor is fitted with a stirring
element which consists of a drive shaft and blade forming a
paddle, B. The blade passes through the diameter of the shaft so
that the bottom of the blade is flush with the bottom of the shaft.
The shaft is positioned so that its axis is within 2 mm of the axis
of the vessel and the lower edge of the blade is 23 to 27 mm from
the inside bottom of the vessel. The apparatus operates in such a
way that the paddle rotates smoothly and without significant
wobble.
A water-bath set to maintain the dissolution medium at 36.5° to
37.5°. The bath liquid is kept in constant and smooth motion
during the test. The vessel is securely clamped in the water-bath
in such a way that the displacement vibration from other
equipment, including the water circulation device, is minimised.
speed of rotation of the paddle within 4 per cent of that specified
in the individual monograph. The motor is fitted with a stirring
element which consists of a drive shaft and blade forming a
paddle, B. The blade passes through the diameter of the shaft so
that the bottom of the blade is flush with the bottom of the shaft.
The shaft is positioned so that its axis is within 2 mm of the axis
of the vessel and the lower edge of the blade is 23 to 27 mm from
the inside bottom of the vessel. The apparatus operates in such a
way that the paddle rotates smoothly and without significant
wobble.
A water-bath set to maintain the dissolution medium at 36.5° to
37.5°. The bath liquid is kept in constant and smooth motion
during the test. The vessel is securely clamped in the water-bath
in such a way that the displacement vibration from other
equipment, including the water circulation device, is minimised.
DTSLO IS
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4
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Specification of paddle used in dissolution test apparatus
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Specification of paddle used in dissolution test apparatus
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(Ap paratus 2
e The assembly is the same as in Apparatus 1 except that in the
stirring element the paddle is replaced by a basket, D.
e The metallic shaft rotates smoothly and without significant
wobble.
e The basket consists of two components.
e Thetop part, with a vent, is attached to the shaft C, it is fitted with
three spring clips, or other suitable means, that allow removal of the
lower part for introduction of the preparation under examination and
tl
hat firmly hold the lower part of the basket concentric with the axis
of the vessel during rotation.
e The lower detachable part of the basket is made of welded-steam
cloth, with a wire thickness of 0.254 mm diameter and with 0.381mm
square openings, formed into a cylinder with narrow rim of sheet
metal around the top and the bottom
e The basket may be plated with a 2.5m m layer of gold for use
with acidic media. The distance between the inside bottom of the
vessel and the basket is maintained at 23 to 27mm during the test.
e The assembly is the same as in Apparatus 1 except that in the
stirring element the paddle is replaced by a basket, D.
e The metallic shaft rotates smoothly and without significant
wobble.
e The basket consists of two components.
e Thetop part, with a vent, is attached to the shaft C, it is fitted with
three spring clips, or other suitable means, that allow removal of the
lower part for introduction of the preparation under examination and
tl
hat firmly hold the lower part of the basket concentric with the axis
of the vessel during rotation.
e The lower detachable part of the basket is made of welded-steam
cloth, with a wire thickness of 0.254 mm diameter and with 0.381mm
square openings, formed into a cylinder with narrow rim of sheet
metal around the top and the bottom
e The basket may be plated with a 2.5m m layer of gold for use
with acidic media. The distance between the inside bottom of the
vessel and the basket is maintained at 23 to 27mm during the test.
L
Specification of basket used in dissolution test apparatus
Specification of basket used in dissolution test apparatus
(D
e Use the dissolution medium specified in the individual
issolution medium
monograph.
e 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.
e The dissolution medium should be deaerated prior to testing.
Time
e 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.
e If two or more times are specified, specimen are to be withdrawn
only at the stated times, within a tolerance of + 2 per cent.
e Use the dissolution medium specified in the individual
issolution medium
monograph.
e 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.
e The dissolution medium should be deaerated prior to testing.
Time
e 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.
e If two or more times are specified, specimen are to be withdrawn
only at the stated times, within a tolerance of + 2 per cent.
Dissolution test apparatus
(Method
Conventional and prolonged-release solid dosage forms
Place the stated volume of the dissolution medium, free from
dissolved air, into the vessel of the apparatus.
Assemble the apparatus and warm the dissolution medium to
36.5° to 37.5°.
Unless otherwise stated, place one dosage unit in the apparatus,
taking care to exclude air bubbles from the surface of the
dosage unit.
When Apparatus | is used, allow the tablet or capsule to sink to
the bottom of the vessel prior to the rotation of the paddle.
A suitable device such as a wire of glass helix may be used to
keep horizontal at the bottom of the vessel tablets or capsules
that would otherwise float.
Conventional and prolonged-release solid dosage forms
Place the stated volume of the dissolution medium, free from
dissolved air, into the vessel of the apparatus.
Assemble the apparatus and warm the dissolution medium to
36.5° to 37.5°.
Unless otherwise stated, place one dosage unit in the apparatus,
taking care to exclude air bubbles from the surface of the
dosage unit.
When Apparatus | is used, allow the tablet or capsule to sink to
the bottom of the vessel prior to the rotation of the paddle.
A suitable device such as a wire of glass helix may be used to
keep horizontal at the bottom of the vessel tablets or capsules
that would otherwise float.
e\
When Apparatus 2 is used, place the tablet or capsule in a dry
basket at the beginning of each test.
Lower the basket into position before rotation.
Operate the apparatus immediately at the speed of rotation
specified in the individual monograph.
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 anal as directed in the individual monograph.
Repeat the whole operation five times.
When Apparatus 2 is used, place the tablet or capsule in a dry
basket at the beginning of each test.
Lower the basket into position before rotation.
Operate the apparatus immediately at the speed of rotation
specified in the individual monograph.
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 anal as directed in the individual monograph.
Repeat the whole operation five times.
o Where two or more tablets or capsules are directed to be
placed together in the apparatus, carry out six replicate tests.
e For each of the tablet or capsule tested, calculate the amount
of dissolved active ingredient in solution as a percentage of
the stated amount where two or more tablets or capsules are
placed together, determine for each test the amount of active
ingredient in solution per tablet or capsules and calculate as a
percentage of the stated amount.
Acceptance criteria
e Conventional-release dosage forms
e Unless otherwise specified, the requirements are met if the
quantities of active substance dissolved from the dosage
units conform to Table 1.
placed together in the apparatus, carry out six replicate tests.
e For each of the tablet or capsule tested, calculate the amount
of dissolved active ingredient in solution as a percentage of
the stated amount where two or more tablets or capsules are
placed together, determine for each test the amount of active
ingredient in solution per tablet or capsules and calculate as a
percentage of the stated amount.
Acceptance criteria
e Conventional-release dosage forms
e Unless otherwise specified, the requirements are met if the
quantities of active substance dissolved from the dosage
units conform to Table 1.
Table 1
Level Number Acceptance criteria
tested
S, 6 Each unit is not less than D* + 5 per
cent**.
S, 6 Average of 12 units (S, +S,) is equal to
or greater than D. and no unit is less
than D-15 per cent**.
S, 12 Average of 24 units (S,+S,+S,)is equal
to or greater than D, not, More than 2
units are less than D — 15 per cent** and
no unit is less than D — 25 per cent**.
*D is the amount of dissolved active ingredient specified in the individual
monograph, expressed as a percentage of the labelled content.
**Percentages of the labelled content.
Level Number Acceptance criteria
tested
S, 6 Each unit is not less than D* + 5 per
cent**.
S, 6 Average of 12 units (S, +S,) is equal to
or greater than D. and no unit is less
than D-15 per cent**.
S, 12 Average of 24 units (S,+S,+S,)is equal
to or greater than D, not, More than 2
units are less than D — 15 per cent** and
no unit is less than D — 25 per cent**.
*D is the amount of dissolved active ingredient specified in the individual
monograph, expressed as a percentage of the labelled content.
**Percentages of the labelled content.
If the results do not conform to the requirements at stage
S, given in the table, continue testing with additional
dosage units through stages S, and S, unless the results
conform at stage S,.
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.
e Correction factors should not be greater than 25 per cent of
the stated amount.
S, given in the table, continue testing with additional
dosage units through stages S, and S, unless the results
conform at stage S,.
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.
e Correction factors should not be greater than 25 per cent of
the stated amount.
(7
e Prolonged-release dosage forms
e Unless otherwise specified, the requirements are met if the
quantities of active substance dissolved from the dosage units
conform to Table 2.
e If the results do not conform to the requirements at stage Ll
given in the table, continue testing with additional dosage
units through stages L2 and L3 unless the results conform at
stage L2.
e The limits embrace each value of D, the amount dissolved at
each specified dosing interval.
e Where more than one range is specified, the acceptance
criteria apply to each range.
e Prolonged-release dosage forms
e Unless otherwise specified, the requirements are met if the
quantities of active substance dissolved from the dosage units
conform to Table 2.
e If the results do not conform to the requirements at stage Ll
given in the table, continue testing with additional dosage
units through stages L2 and L3 unless the results conform at
stage L2.
e The limits embrace each value of D, the amount dissolved at
each specified dosing interval.
e Where more than one range is specified, the acceptance
criteria apply to each range.
po
Level
L
F
Number
tested
6
Table 2
Acceptance criteria
No individual value lies outside each of
the stated ranges and no individual value
is less than the stated amount at the final
test time.
The average value of the 12 units (L, +
L,) lies within each of the stated ranges
and is not less than the stated amount at
the final test time: none is more than 10
per cent of labelled content outside each
of the stated ranges: and none is more
than 10 per cent of labelled amount below
the stated amount at the final test time.
À
Level
L
F
Number
tested
6
Table 2
Acceptance criteria
No individual value lies outside each of
the stated ranges and no individual value
is less than the stated amount at the final
test time.
The average value of the 12 units (L, +
L,) lies within each of the stated ranges
and is not less than the stated amount at
the final test time: none is more than 10
per cent of labelled content outside each
of the stated ranges: and none is more
than 10 per cent of labelled amount below
the stated amount at the final test time.
À
x
Level Number Acceptance criteria
tested
Ly 12 The average value of the 24 units (L, +
L, + L,) lies within each of the stated
ranges, and is not less than the stated
amount at the final test time: not more
than 2 of the 24 units are more than 10
per cent of labelled content outside each
of the stated ranges: not more than 2 of
the 24 units are more than 10 per cent of
labelled content below the stated
amount at the final test time: and none
of the units is more than 20 per cent of
labelled content outside each of the
stated ranges or more than 20 per cent
of labelled content below the stated
amount at the final test time
Level Number Acceptance criteria
tested
Ly 12 The average value of the 24 units (L, +
L, + L,) lies within each of the stated
ranges, and is not less than the stated
amount at the final test time: not more
than 2 of the 24 units are more than 10
per cent of labelled content outside each
of the stated ranges: not more than 2 of
the 24 units are more than 10 per cent of
labelled content below the stated
amount at the final test time: and none
of the units is more than 20 per cent of
labelled content outside each of the
stated ranges or more than 20 per cent
of labelled content below the stated
amount at the final test time
(o
Modified-release dosage forms
e Use method A or Method B.
Method A
e Acid stage.
e Place 750 ml of 0.1M hydrochloric acid in the vessel, and
assemble the apparatus.
e Warm the dissolution medium to 36.5% to 37.5°.
e Place one dosage unit in the apparatus, cover the vessel and
operate the apparatus at the specified rate.
e After 2 hours of operation in the acid medium, withdraw an
aliquot of the liquid and proceed immediately as directed under
Buffer stage.
e Perform the analysis of the aliquot using a suitable assay/
analytical method.
Modified-release dosage forms
e Use method A or Method B.
Method A
e Acid stage.
e Place 750 ml of 0.1M hydrochloric acid in the vessel, and
assemble the apparatus.
e Warm the dissolution medium to 36.5% to 37.5°.
e Place one dosage unit in the apparatus, cover the vessel and
operate the apparatus at the specified rate.
e After 2 hours of operation in the acid medium, withdraw an
aliquot of the liquid and proceed immediately as directed under
Buffer stage.
e Perform the analysis of the aliquot using a suitable assay/
analytical method.
A Buffer stage.
e Complete the operations of adding the buffer and adjusting the
pH within 5 minutes.
e With the apparatus operating at the rate specified, add to the
medium in the vessel 250 ml of a 0.2 M solution of trisodium
phosphate dodecahydrate that has been warmed to 36.5% to
37.5%
e Adjust, if necessary, with 2M hydrochloric acid or 2M sodium
hydroxide to a pH of 6.8 + 0.05. 2M hydrochloric acid or 2M
sodium hydroxide to a pH of 6.8 + 0.05.
Method B
e Acid stage.
e Place 1000 ml of 0.1M hydrochloric acid in the vessel and
assemble the apparatus.
e Complete the operations of adding the buffer and adjusting the
pH within 5 minutes.
e With the apparatus operating at the rate specified, add to the
medium in the vessel 250 ml of a 0.2 M solution of trisodium
phosphate dodecahydrate that has been warmed to 36.5% to
37.5%
e Adjust, if necessary, with 2M hydrochloric acid or 2M sodium
hydroxide to a pH of 6.8 + 0.05. 2M hydrochloric acid or 2M
sodium hydroxide to a pH of 6.8 + 0.05.
Method B
e Acid stage.
e Place 1000 ml of 0.1M hydrochloric acid in the vessel and
assemble the apparatus.
Warm the dissolution medium to 36.5% to 37.5°.
Place one dosage unit in the apparatus, cover the vessel and
operate the apparatus at the specified rate.
After 2 hours of operation in the acid medium, withdraw an
aliquot of the liquid and proceed immediately as directed under
Buffer stage.
Perform the analysis of the aliquot using a suitable assay
method.
Buffer stage.
Use buffer that has previously been warmed to 36.5% to 37.5°.
Drain the acid from the vessel and add 1000 ml of pH 6.8
phosphate buffer, prepared by mixing 3 volumes of 0.1M
hydrochloric acid with 1 volume of 0.2 M solution of trisodium
phosphate dodecahydrate and adjusting, if necessary, with 2M
hydrochloric acid or 2M sodium hydroxide to a pH of 6.8 + 0.05.
Place one dosage unit in the apparatus, cover the vessel and
operate the apparatus at the specified rate.
After 2 hours of operation in the acid medium, withdraw an
aliquot of the liquid and proceed immediately as directed under
Buffer stage.
Perform the analysis of the aliquot using a suitable assay
method.
Buffer stage.
Use buffer that has previously been warmed to 36.5% to 37.5°.
Drain the acid from the vessel and add 1000 ml of pH 6.8
phosphate buffer, prepared by mixing 3 volumes of 0.1M
hydrochloric acid with 1 volume of 0.2 M solution of trisodium
phosphate dodecahydrate and adjusting, if necessary, with 2M
hydrochloric acid or 2M sodium hydroxide to a pH of 6.8 + 0.05.
This may also be done by removing from the apparatus the
vessel containing the acid and replacing it with another vessel
containing the buffer and transferring the dosage unit to the
vessel containing the buffer.
Continue to operate the apparatus for 45 minutes, or for the
specified time.
At the end of this period, withdraw an aliquot of the liquid and
perform the analysis using a suitable assay method.
Acceptance criteria
Acid stage.
Unless otherwise specified, the requirements of this part of the
test are met if the quantities, based on the percentage of the
labelled content of active substance dissolved from the units
tested conform to Table 3.
vessel containing the acid and replacing it with another vessel
containing the buffer and transferring the dosage unit to the
vessel containing the buffer.
Continue to operate the apparatus for 45 minutes, or for the
specified time.
At the end of this period, withdraw an aliquot of the liquid and
perform the analysis using a suitable assay method.
Acceptance criteria
Acid stage.
Unless otherwise specified, the requirements of this part of the
test are met if the quantities, based on the percentage of the
labelled content of active substance dissolved from the units
tested conform to Table 3.
po
e Continue the testing through the 3 levels unless the results of
both acid and buffer stages conform at an earlier level.
Table 3
Level Number Acceptance criteria
tested
A, 6 No individual value exceeds 10 per
cent dissolved.
As 6 The average value of the 12 units (A,
+ A,) is not more than 10 per cent
dissolved. and no individual unit is
greater than 25 per cent dissolved.
As 12 The average value of the 24 units (A,
+ A, + Aj) is not more than 10 per
cent aaa, and no individual unit
is greater than 25 per cent dissolved.
À
e Continue the testing through the 3 levels unless the results of
both acid and buffer stages conform at an earlier level.
Table 3
Level Number Acceptance criteria
tested
A, 6 No individual value exceeds 10 per
cent dissolved.
As 6 The average value of the 12 units (A,
+ A,) is not more than 10 per cent
dissolved. and no individual unit is
greater than 25 per cent dissolved.
As 12 The average value of the 24 units (A,
+ A, + Aj) is not more than 10 per
cent aaa, and no individual unit
is greater than 25 per cent dissolved.
À
fs
Buffer stage.
Unless otherwise specified, the requirements of this part of the
test are met if the quantities, based on the percentage of the
labelled content of active substance dissolved from the units
tested conform to Table 4.
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 4 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 labelled content.
Buffer stage.
Unless otherwise specified, the requirements of this part of the
test are met if the quantities, based on the percentage of the
labelled content of active substance dissolved from the units
tested conform to Table 4.
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 4 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 labelled content.
a Table 4
Level Number Acceptance criteria
tested
B, 6 No unit is less than D + 5 per cent*
B, 6 The average value of the 12 units (B,
+ B,) is equal to or greater than D,and
no unit is less than D — 15 per cent*.
B, 12 The average value of 24 units (B, +
B, + B,) is equal to or greater than
D, not more than 2 units are less than
D — 15 per cent*, and no unit is less
than D — 25 per cent*.
* percentages of the labelled content.
L
Level Number Acceptance criteria
tested
B, 6 No unit is less than D + 5 per cent*
B, 6 The average value of the 12 units (B,
+ B,) is equal to or greater than D,and
no unit is less than D — 15 per cent*.
B, 12 The average value of 24 units (B, +
B, + B,) is equal to or greater than
D, not more than 2 units are less than
D — 15 per cent*, and no unit is less
than D — 25 per cent*.
* percentages of the labelled content.
L
( VINI.Contents of Packaged Dosage Forms:
e Select a sample of 10 containers and count the number of
capsules or tablets in each container.
e The average number of the contents in the 10 containers is not
less than the labelled amount and the number in any single
container is not less than 98 per cent and not more than 102 per
cent of the labelled amount.
e Ifthis requirements is not met, count the number of the contents
in 10 additional containers.
e The average number in the 20 containers is not less than the
labelled 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
labelled amount.
IX. Content labelling requirement:
e All official tablets must be labelled to express the quantity of
each active ingredient in each dosage unit.
e Select a sample of 10 containers and count the number of
capsules or tablets in each container.
e The average number of the contents in the 10 containers is not
less than the labelled amount and the number in any single
container is not less than 98 per cent and not more than 102 per
cent of the labelled amount.
e Ifthis requirements is not met, count the number of the contents
in 10 additional containers.
e The average number in the 20 containers is not less than the
labelled 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
labelled amount.
IX. Content labelling requirement:
e All official tablets must be labelled to express the quantity of
each active ingredient in each dosage unit.
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