QUALITY CONTROL TESTS QUALITY CONTROL TESTS FOR TABLETS AND FOR TABLETS AND

CAPSULESCAPSULES

Quality Control of TabletsQuality Control of Tablets

General Appearance:General Appearance:

-Size, shape, and thickness: -Size, shape, and thickness:

This is important to facilitate packaging This is important to facilitate packaging and to decide which tablet compressing and to decide which tablet compressing machine to use.machine to use.

-Organoleptic properties: -Organoleptic properties:

which include color and odor of the which include color and odor of the tablets.tablets.

Official Standards as per B.P. Official Standards as per B.P. /I.P./ U.S.P./I.P./ U.S.P.

COMPARISON OF DIFFERENT COMPARISON OF DIFFERENT PHARMACOPOEIAL QUALITY CONTROL PHARMACOPOEIAL QUALITY CONTROL TESTS TESTS

BRITISH PHARMACOPOEIABRITISH PHARMACOPOEIA FOR ALL TABLETS:FOR ALL TABLETS: Content of active ingredientsContent of active ingredients DisintegrationDisintegration Uniformity of contentUniformity of content LabelingLabeling

Uncoated tablet:Uncoated tablet:-Disintegration test-Disintegration test-Uniformity of weight-Uniformity of weight

Effervescent tablet:Effervescent tablet: -Disintegration test-Disintegration test -Uniformity of weight-Uniformity of weight

Coated tablet:Coated tablet:-Disintegration test-Disintegration test-Uniformity of weight-Uniformity of weight

Gastro resistant tablet:Gastro resistant tablet:

-Disintegration test-Disintegration test

Modified release tablet:Modified release tablet:

-Uniformity of weight.-Uniformity of weight.

Dispersible tablet:Dispersible tablet:

-Disintegration test-Disintegration test

-Uniformity of dispersion-Uniformity of dispersion

-Uniformity of weight-Uniformity of weight

INDIAN PHARMACOPOEIAINDIAN PHARMACOPOEIA

Uncoated tablet:Uncoated tablet:

-Uniformity of container content-Uniformity of container content

-Content of active ingredient-Content of active ingredient

-Uniformity of weight-Uniformity of weight

-Uniformity of content-Uniformity of content

-Disintegration test-Disintegration test

Enteric coated tablet:Enteric coated tablet:

-Disintegration test-Disintegration test

Dispersible tablet:Dispersible tablet:

-Uniformity of dispersion-Uniformity of dispersion

-Disintegration-Disintegration

Soluble tablet:Soluble tablet:

-Disintegration test-Disintegration test

Effervescent tablet:Effervescent tablet:

-Disintegration/ Dissolution / Dispersion-Disintegration/ Dissolution / Dispersiontesttest

UNITED STATES PHARMACOPOEIAUNITED STATES PHARMACOPOEIA

Physical tests applicable to tablet formulation:Physical tests applicable to tablet formulation:-Bulk density /Tapped density of powder-Bulk density /Tapped density of powder-Powder fineness-Powder fineness-Loss on drying-Loss on drying-Disintegration test-Disintegration test-Tablet friability-Tablet friability-Dissolution test-Dissolution test-Drug release testing-Drug release testing-Uniformity of dosage form-Uniformity of dosage form-Container permeation test-Container permeation test-Labeling of inactive ingredients-Labeling of inactive ingredients

Official and unofficial tests:Official and unofficial tests: Official Tests: Official Tests:

Weight variation, disintegration, Weight variation, disintegration, dissolution, drug content. dissolution, drug content.

Non-Official Tests: Non-Official Tests:

Hardness, friability.Hardness, friability.

I- I- Non official tests:Non official tests:

Hardness Hardness (crushing strength):(crushing strength):It is the load required to crush the tablet when It is the load required to crush the tablet when

placed on its edgeplaced on its edge..

Why do we measure hardness?Why do we measure hardness? To determine the need for pressure To determine the need for pressure

adjustments on the tableting machine. adjustments on the tableting machine. Hardness can affect the disintegration. So Hardness can affect the disintegration. So

if the tablet is too hard, it may not if the tablet is too hard, it may not disintegrate in the required period of time. disintegrate in the required period of time. And if the tablet is too soft, it will not And if the tablet is too soft, it will not withstand the handling during subsequentwithstand the handling during subsequent

processing such as coating or processing such as coating or packagingpackaging..

>In general, if the tablet hardness is too >In general, if the tablet hardness is too high, we first check its disintegration high, we first check its disintegration before rejecting the patch. And if the before rejecting the patch. And if the disintegration is within limit, we accept the disintegration is within limit, we accept the patch.patch.

>If H. is high + disintegration is within time >If H. is high + disintegration is within time è accept the batch.è accept the batch.

Factors Affecting the Hardness:Factors Affecting the Hardness:Compression of the tablet and Compression of the tablet and

compressive force. compressive force. Amount of binder. (More binder à more Amount of binder. (More binder à more

hardness) hardness) Method of granulation in preparing the Method of granulation in preparing the

tablet (wet method gives more hardness tablet (wet method gives more hardness than direct method, Slugging method gives than direct method, Slugging method gives the best hardness).the best hardness).

Limits:Limits: 5 kilograms minimum and 8 kilograms 5 kilograms minimum and 8 kilograms

maximum.maximum.

>Make hardness test on 5 tablets and then >Make hardness test on 5 tablets and then take the average hardness.take the average hardness.

FriabilityFriability::

It is the tendency of tablets to powder, It is the tendency of tablets to powder, chip, or fragment and this can affect the chip, or fragment and this can affect the elegance appearance, consumer elegance appearance, consumer acceptance of the tablet, and also add to acceptance of the tablet, and also add to tablet’s weight variation or content tablet’s weight variation or content uniformity problems.uniformity problems.

Friability is a property that is related to Friability is a property that is related to the hardness of the tablet. the hardness of the tablet.

An instrument called friabilator is used to An instrument called friabilator is used to evaluate the ability of the tablet to evaluate the ability of the tablet to withstand abrasion in packaging, withstand abrasion in packaging, handling, and shipping. handling, and shipping.

Procedure:Procedure:1. Weigh 20 tab altogether = W11. Weigh 20 tab altogether = W1 2. Put these tablets in the friabilator and adjust the 2. Put these tablets in the friabilator and adjust the

instrument at 100 rpm (i.e. = 25 rpm for 4 min)instrument at 100 rpm (i.e. = 25 rpm for 4 min) 3. Weigh the 20 tablets (only the intact ones) = W23. Weigh the 20 tablets (only the intact ones) = W2 4. Friability (% loss) = 4. Friability (% loss) = It must be less than or equal to1% but if more we It must be less than or equal to1% but if more we

do not reject the tablets as this test is non-do not reject the tablets as this test is non-official.official.

Perform this test using 20 tablets that were used Perform this test using 20 tablets that were used first in the weight variation testfirst in the weight variation test

II- II- Official Tests:Official Tests:

Disintegration:Disintegration:

It is the time required for the tablet to break It is the time required for the tablet to break into particles, the disintegration test is a into particles, the disintegration test is a measure only of the time required under a measure only of the time required under a given set of conditions for a group of given set of conditions for a group of tablets to disintegrate into particles. tablets to disintegrate into particles.

Liquids used in Liquids used in disintegrationdisintegration

Water, Water, simulated gastric fluid simulated gastric fluid

(PH = 1.2 HCl), (PH = 1.2 HCl), or Simulated intestinal or Simulated intestinal

fluid (PH = 7.5, fluid (PH = 7.5, KH2PO4 (phosphate KH2PO4 (phosphate buffer) + pencreatin buffer) + pencreatin enzyme +NaOH)enzyme +NaOH)

Limits:Limits:

For Uncoated tablets:For Uncoated tablets:

MediumMedium TemperTemperature ature

Time Time limit limit

According to According to U.S.P.U.S.P.

Simulated Simulated gastric gastric fluidfluid

37oC 37oC Not Not exceed exceed 30min30min

According to According to B.P.B.P.

waterwater 37oC 37oC Not Not exceed exceed 15min15min

U.S.P. method for uncoated tablets:U.S.P. method for uncoated tablets:Start the disintegration test on 6 tablets. Start the disintegration test on 6 tablets. If one or two tablets from the 6 tablets fail If one or two tablets from the 6 tablets fail

disintegrate completely within 30min disintegrate completely within 30min repeat the same test on another 12 tablet. repeat the same test on another 12 tablet. (i.e. the whole test will consume 18 (i.e. the whole test will consume 18 tablets). tablets).

Not less then 16 tablets disintegrate Not less then 16 tablets disintegrate completely within the time completely within the time

if more then two tablets (from the 18) fail if more then two tablets (from the 18) fail to disintegrate, the batch must be rejected. to disintegrate, the batch must be rejected.

For Coated tablets:For Coated tablets:1. To remove or dissolve the coat, immerse 1. To remove or dissolve the coat, immerse

the tablet in distilled water for 5min.the tablet in distilled water for 5min.Put the tablet in the apparatus in water or Put the tablet in the apparatus in water or

HCL for 30min at 37oC (according to the HCL for 30min at 37oC (according to the U.S.P). If not disintegrated, put in intestinal U.S.P). If not disintegrated, put in intestinal fluid.fluid.

>If one or two tablets fail to disintegrate, >If one or two tablets fail to disintegrate, repeat on 12 tablets. So 16 tablets from the repeat on 12 tablets. So 16 tablets from the 18 must completely disintegrate within the 18 must completely disintegrate within the time >>if two or more not disintegrated the time >>if two or more not disintegrated the batch is rejected.batch is rejected.

U.S.P. Method for Enteric coated tablets:U.S.P. Method for Enteric coated tablets:1. Put in distilled water for five minutes to 1. Put in distilled water for five minutes to

dissolve the coat.dissolve the coat.2. Then put in simulated gastric fluid (0.1M 2. Then put in simulated gastric fluid (0.1M

HCL) for one hour.HCL) for one hour.3. Then put in simulated intestinal fluid for 3. Then put in simulated intestinal fluid for

two hours.two hours. If one or two tablets fail to disintegrate, If one or two tablets fail to disintegrate,

repeat this test on another 12 tablets. So 16 repeat this test on another 12 tablets. So 16 tablets from 18 should completely tablets from 18 should completely disintegrate. If more than two fail to disintegrate. If more than two fail to disintegrate the patch must be rejected.disintegrate the patch must be rejected.

B.P. method for Enteric coated tablets:B.P. method for Enteric coated tablets:1. Put in distilled water for five minutes to 1. Put in distilled water for five minutes to

dissolve the coat.dissolve the coat.2. Put in simulated gastric fluid for two 2. Put in simulated gastric fluid for two

hours (emptying time).hours (emptying time).3. Put in phosphate buffer (PH 6.8) for one 3. Put in phosphate buffer (PH 6.8) for one

hour.hour.4. If one or two tablets fail to disintegrate 4. If one or two tablets fail to disintegrate

repeat on 12 tablets. So 16 tablets should repeat on 12 tablets. So 16 tablets should disintegrate. If more than two tables fail to disintegrate. If more than two tables fail to disintegrate reject the batch.disintegrate reject the batch.

Weight Variation (uniformity of weight) of Weight Variation (uniformity of weight) of tablets:tablets:

1.1. Weigh 20 tablet selected at random, Weigh 20 tablet selected at random, each one individuallyeach one individually . X1, X2, X3… Xz . X1, X2, X3… Xz

2.2. Determine the average weight. X= Determine the average weight. X= (X1+X2 +X3+…+ Xz)/20(X1+X2 +X3+…+ Xz)/20

Limits according to U.S.PLimits according to U.S.P · Weight of tablet 130 mg or less then · Weight of tablet 130 mg or less then

%error = ±10%%error = ±10% · Weight of tablet 130-324 mg then · Weight of tablet 130-324 mg then

%error = ±7.5%%error = ±7.5% · Weight of tablet 324 mg or more then · Weight of tablet 324 mg or more then

%error = ±5%%error = ±5%

Limit:Limit:Upper limit = average weight + (average Upper limit = average weight + (average

weight * %error)weight * %error)Lower limit = average weight - (average Lower limit = average weight - (average

weight * %error)weight * %error)The individual weights are compared with The individual weights are compared with

the upper and lower limits.the upper and lower limits.

>>Not more than two of the tablets differ from >>Not more than two of the tablets differ from the average weight by more than the % the average weight by more than the % error listed, and no tablet differs by more error listed, and no tablet differs by more than double that percentage.than double that percentage.

Quality control tests of capsulesQuality control tests of capsules

B.P. method for disintegration of capsules:B.P. method for disintegration of capsules: Introduce one capsule into each tube and suspend the apparatus in a Introduce one capsule into each tube and suspend the apparatus in a

beaker containing 600 ml water @ 37oC. beaker containing 600 ml water @ 37oC. If hard capsules float on the surface of the water, the discs may be If hard capsules float on the surface of the water, the discs may be

added. added. Operate the apparatus for 30 minutes; remove the assembly from the Operate the apparatus for 30 minutes; remove the assembly from the

liquid. liquid.

>The capsules pass the test if >The capsules pass the test if No residue remains on the screen of the apparatus or, No residue remains on the screen of the apparatus or, If a residue remains, it consists of fragments of shell or, If a residue remains, it consists of fragments of shell or, Is a soft mass with no palpable core. Is a soft mass with no palpable core. If the disc is used, any residue remaining on its lower surface should If the disc is used, any residue remaining on its lower surface should

only consist of fragments of shell only consist of fragments of shell

Uniformity of Weight of capsules:Uniformity of Weight of capsules:

It is to be done on 20 capsules.It is to be done on 20 capsules.Limit:Limit:

Not more than two of the individual weights Not more than two of the individual weights deviate from the average weight by more deviate from the average weight by more than the percentage deviation shown in the than the percentage deviation shown in the table, and none deviates by more than table, and none deviates by more than twice that percentage.twice that percentage.

Average Weight of Average Weight of CapsuleCapsule

Percentage Deviation Percentage Deviation

Less than 300 mg Less than 300 mg 1010

300 mg or more 300 mg or more 7.57.5