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CONTENTS• Introduction

• Quality control tests of TABLETS

• Quality control tests of CAPSULES

INTRODUCTION

Quality control, or QC for short, is a process by which entities review the quality of all factors involved in production.

Quality Control Tests OfTABLETS

QUALITY CONTROLQUALITY CONTROLTESTS OFTESTS OFTABLETSTABLETS

PHYSICAL TESTSPHYSICAL TESTS CHEMICAL TESTSCHEMICAL TESTS

3: Friability Test3: Friability Test

1: Hardness Test1: Hardness Test2: Tablet Thickness2: Tablet Thickness

andandDiameter Diameter

3: Dissolution Test3: Dissolution Test

1: Content Uniformity1: Content Uniformity 2: Assay2: Assay

4: Disintegration 4: Disintegration TestTest

5: Weight Variation5: Weight VariationTestTest

HardnessHardness It is defined as the force required to break a It is defined as the force required to break a

tablet in a diametric compression test. tablet in a diametric compression test. Tablet requires a certain amount of strength Tablet requires a certain amount of strength

or hardness and resistance to friability to or hardness and resistance to friability to withstand mechanical shakes of handling in withstand mechanical shakes of handling in manufacture, packaging and shipping.manufacture, packaging and shipping.

Tablet Hardness Test is performed to check Tablet Hardness Test is performed to check that the manufactured tablet is of desired that the manufactured tablet is of desired hardness.hardness.

Hardness TestersHardness Testers

1.1. Strong-CobbStrong-Cobb2.2. Stokes-MonsantoStokes-Monsanto3.3. EurekaEureka4.4. PfizerPfizer

1:Strong-Cobb1:Strong-Cobb• The tablet is The tablet is

placed between placed between two jaws that two jaws that crush the tablet. crush the tablet.

• The machine The machine measures the measures the force applied to force applied to the tablet and the tablet and detects when it detects when it fractures.fractures.

2:Stokes-Monsanto2:Stokes-Monsanto

Tube like structure Tube like structure in which tablet is in which tablet is placed.placed.

Force in kg is Force in kg is required to break required to break tablet.tablet.

4kg is general 4kg is general rangerange

3: Eureka3: Eureka The breaking force is applied by a beam The breaking force is applied by a beam

fastened to one end to a pivotfastened to one end to a pivot The motor moves a weight along the beam at The motor moves a weight along the beam at

a constant speed and increases the force a constant speed and increases the force against the tablet on which the other end of against the tablet on which the other end of the beam reststhe beam rests

When the tablet breaks, a microswitch is When the tablet breaks, a microswitch is activated that stops the motoractivated that stops the motor

An indicator fastened to the weight shows An indicator fastened to the weight shows the breaking strength on scale in kilogram the breaking strength on scale in kilogram units units

Eureka instrument

4: Pfizer4: Pfizer

Factors Affecting HardnessFactors Affecting Hardness Pressure applied during the compressionPressure applied during the compression Cohesive forces between ingredients Cohesive forces between ingredients

especially binder have more cohesive especially binder have more cohesive forcesforces

Density Density

Thickness and DiameterThickness and Diameter Tablet thickness and diameter tests are also Tablet thickness and diameter tests are also

very important qc testsvery important qc tests Very thick tablet affects packaging either in Very thick tablet affects packaging either in

blister or plastic containerblister or plastic container The thickness for majority of tablets may vary The thickness for majority of tablets may vary

from 2mm to 4mmfrom 2mm to 4mm The diameter of tablets may vary from 4mm to The diameter of tablets may vary from 4mm to

13mm13mm

Instruments usedInstruments used

For diameter: Vernier CalipersFor diameter: Vernier Calipers

For thickness: Micrometer Screw Gauge For thickness: Micrometer Screw Gauge

Vernier CallipersVernier Callipers

Micrometer Screw GaugeMicrometer Screw Gauge

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 the Friability is a property that is related to the hardness of the tablet. 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, handling, withstand abrasion in packaging, handling, and shipping.and shipping.

FriabilatorFriabilator►Friabilator is a round drum Friabilator is a round drum ►It has diameter of 2.87mm and depth of It has diameter of 2.87mm and depth of

38mm38mm►In diameter a horizontal axis is presentIn diameter a horizontal axis is present►Friabilator is connected to timer to indicate Friabilator is connected to timer to indicate

its rotationsits rotations►It is rotated in clockwise directionIt is rotated in clockwise direction

Timer

Rotating drum

Test MethodTest Method►Weigh 20 tab altogether = W1Weigh 20 tab altogether = W1►Put these tablets in the friabilator and adjust Put these tablets in the friabilator and adjust

the instrument at 100 rpm (i.e. = 25 rpm for 4 the instrument at 100 rpm (i.e. = 25 rpm for 4 min)min)

►Weigh the 20 tablets (only the intact ones) = Weigh the 20 tablets (only the intact ones) = W2W2

►The difference between W1 and W2 gives The difference between W1 and W2 gives weight loss (i.e. Friability)weight loss (i.e. Friability)

►Weight loss of 1-5% is acceptable Weight loss of 1-5% is acceptable

DisintegrationDisintegration For most tablets , the first important step towards For most tablets , the first important step towards

formation of solution is breakdown of the tablet formation of solution is breakdown of the tablet into smaller particles or granules , this process is into smaller particles or granules , this process is known as disintegration.known as disintegration.

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

Disintegration apparatusDisintegration apparatus The apparatus consists of;The apparatus consists of; Basket rack assemblyBasket rack assembly A suitable vessel for the immersion liquidA suitable vessel for the immersion liquid A thermostatic arrangement for heating the fluid A thermostatic arrangement for heating the fluid

between 35°C and 39°Cbetween 35°C and 39°C A device for raising and lowering the basket in A device for raising and lowering the basket in

the immersion fluid at a constant frequency rate the immersion fluid at a constant frequency rate between 28 and 32 cpm through a distance of between 28 and 32 cpm through a distance of not less than 5cm and not more than 6cm not less than 5cm and not more than 6cm

BASKET RACK ASSEMBLYBASKET RACK ASSEMBLY:- It consists of;:- It consists of; Six open ended glass tubes each 7.75cm long and Six open ended glass tubes each 7.75cm long and

having an inside diameter of approximately 21.5mm having an inside diameter of approximately 21.5mm and a wall 2mm thickand a wall 2mm thick

The tubes are held in a vertical position by two The tubes are held in a vertical position by two plastic plates plastic plates

Each tube is provided with a slotted and perforated Each tube is provided with a slotted and perforated cylindrical diskcylindrical disk

Glass Tubes

Disintegration test is Disintegration test is performed with different types performed with different types

of tabletsof tablets1.1. Uncoated tabletsUncoated tablets

2.2. Coated tabletsCoated tablets

3.3. Enteric coated tabletsEnteric coated tablets

4.4. Buccal tabletsBuccal tablets

5.5. Sublingual tabletsSublingual tablets

Different liquid mediums are Different liquid mediums are used in disintegration testused in disintegration test

WaterWater Simulated gastric fluid (PH= 1.2)Simulated gastric fluid (PH= 1.2) Simulated intestinal fluid (PH= 7.5)Simulated intestinal fluid (PH= 7.5)

SIMULATED GASTRIC FLUIDSIMULATED GASTRIC FLUID Sodium chloride -------------------- 2gmSodium chloride -------------------- 2gm Pepsin -------------------------------- 3.2gmPepsin -------------------------------- 3.2gm Hydrochloric acid ------------------ 7mlHydrochloric acid ------------------ 7ml Water (q.s to make) --------------- 1000mlWater (q.s to make) --------------- 1000ml

SIMULATED INTESTINAL FLUIDSIMULATED INTESTINAL FLUID Potassium phosphate ----------------- 6.8gmPotassium phosphate ----------------- 6.8gm Pancreatin -------------------------------- 10gmPancreatin -------------------------------- 10gm Sodium hydroxide ---------------------- 190mlSodium hydroxide ---------------------- 190ml Water (q.s to make) --------------- 1000mlWater (q.s to make) --------------- 1000ml

1: Test method for Uncoated tablets1: Test method for Uncoated tablets Place 1 tablet in each of the 6 tubes of the basket, Place 1 tablet in each of the 6 tubes of the basket,

add a disk to each tubeadd a disk to each tube Use water as immersion fluid maintained at 37°CUse water as immersion fluid maintained at 37°C If one or two tablets from the 6 tablets fail If one or two tablets from the 6 tablets fail

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

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

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

2: Test method for coated tablets2: Test method for coated tablets

Place 1 tablet in each of the 6 tubes of the basket, Place 1 tablet in each of the 6 tubes of the basket, add a disk to each tubeadd a disk to each tube

To remove or dissolve the coat, immerse the basket To remove or dissolve the coat, immerse the basket in distilled water for 5min.in distilled water for 5min.

Then add a disk to each tube and operate the Then add a disk to each tube and operate the apparatus using simulated gastric fluid maintained at apparatus using simulated gastric fluid maintained at 37°C 37°C

If one or two tablets fail to disintegrate, repeat on If one or two tablets fail to disintegrate, repeat on 12 tablets. 12 tablets.

So 16 tablets from the 18 must completely So 16 tablets from the 18 must completely disintegrate within the time disintegrate within the time

If two or more not disintegrated the batch is If two or more not disintegrated the batch is rejectedrejected

3: Test method for Enteric coated 3: Test method for Enteric coated tabletstablets

Place 1 tablet in each of the 6 tubes of the basket, Place 1 tablet in each of the 6 tubes of the basket, add a disk to each tubeadd a disk to each tube

Put in distilled water for five minutes to dissolve the Put in distilled water for five minutes to dissolve the coat.coat.

Then operate the apparatus without the disks using Then operate the apparatus without the disks using simulated gastric fluid as immersion fluid maintained simulated gastric fluid as immersion fluid maintained at for one hour.at for one hour.

After one hour, lift the basket and observe the After one hour, lift the basket and observe the tablets, the tablets show no evidence of tablets, the tablets show no evidence of disintegration, cracking or softeningdisintegration, cracking or softening

Then add disk to each tube and operate the Then add disk to each tube and operate the apparatus using simulated intestinal fluid apparatus using simulated intestinal fluid maintained at 37°C for two hours.maintained at 37°C for two hours.

If one or two tablets fail to disintegrate, repeat If one or two tablets fail to disintegrate, repeat this test on another 12 tablets. this test on another 12 tablets.

So 16 tablets from 18 should completely So 16 tablets from 18 should completely disintegrate. If more than two fail to disintegrate disintegrate. If more than two fail to disintegrate the batch must be rejected.the batch must be rejected.

4: Test method for Buccal tablets4: Test method for Buccal tablets Place 1 tablet in each of the 6 tubes of the basketPlace 1 tablet in each of the 6 tubes of the basket Use water as immersion fluid maintained at 37°C Use water as immersion fluid maintained at 37°C Operate the apparatus for 4 hoursOperate the apparatus for 4 hours If one or two tablets fail to disintegrate, repeat this If one or two tablets fail to disintegrate, repeat this

test on another 12 tablets. test on another 12 tablets. So 16 tablets from 18 should completely So 16 tablets from 18 should completely

disintegrate. If more than two fail to disintegrate disintegrate. If more than two fail to disintegrate the batch must be rejectedthe batch must be rejected

5: Test method for Sublingual tablets5: Test method for Sublingual tablets

Place 1 tablet in each of the 6 tubes of the basketPlace 1 tablet in each of the 6 tubes of the basket Use water as immersion fluid maintained at 37°C Use water as immersion fluid maintained at 37°C If one or two tablets fail to disintegrate, repeat If one or two tablets fail to disintegrate, repeat

this test on another 12 tablets. this test on another 12 tablets. So 16 tablets from 18 should completely So 16 tablets from 18 should completely

disintegrate. If more than two fail to disintegrate disintegrate. If more than two fail to disintegrate the batch must be rejectedthe batch must be rejected

Factors Affecting DisintegrationFactors Affecting Disintegration Quantity of disintegrating agentQuantity of disintegrating agent CompactnessCompactness Cohesive forces between the ingredientsCohesive forces between the ingredients Hardness Hardness

Weight VariationWeight Variation The actual weight of a tablet is determined by The actual weight of a tablet is determined by

the diameter of the die and the weight the diameter of the die and the weight adjustment cam on the tablet machineadjustment cam on the tablet machine

The weight control on the tablet machine is The weight control on the tablet machine is routinely adjusted at intervals to ensure that routinely adjusted at intervals to ensure that the specified weight is being reproducedthe specified weight is being reproduced

This test is perform to ensure uniform This test is perform to ensure uniform distribution of ingredients throughout batchdistribution of ingredients throughout batch

Test MethodTest Method Take 20 tabletsTake 20 tablets Weigh individually Weigh individually Determine the average weight of 20 tablets Determine the average weight of 20 tablets Compare individual tablet weight to average Compare individual tablet weight to average

weight weight Not more than 2 of the individual weights Not more than 2 of the individual weights

deviate from the average weight by more than deviate from the average weight by more than the percentage deviation the percentage deviation

And none deviates by more than twice that And none deviates by more than twice that percentage.percentage.

Weight variation tolerances for Weight variation tolerances for uncoated tablets in U.S.P XVIIuncoated tablets in U.S.P XVII

5.0 More than 324

7.5 130-324

10.0 130 or less

Percentage Differences Average weight of

Tablet (mg)

Causes of Weight VariationCauses of Weight Variation1.1. Poor flow of granulesPoor flow of granules

2.2. Variation in size of granules due to Variation in size of granules due to improper sievingimproper sieving

3.3. Presence of very fine granulesPresence of very fine granules

4.4. Improper adjustment of machineImproper adjustment of machine

5.5. Improper flow rateImproper flow rate

Content UniformityContent Uniformity• The content uniformity test is used to

ensure that every tablet contains the amount of drug substance intended with little variation among tablets within a batch.

• The individual variation in drug content might result from a failure to maintain the homogeneity of a tablet granulation through the processing steps leading to compression.

Test MethodTest Method

• 30 Tablets are kept aside .

• 10 tablets are assayed .

• 9 Tablets should have %limit of 85-115% of average of tolerances specified in respective monograph .

• If more than 1 Tablet has 85-115% then, 20 Tablets are assayed Not more than 1 Tablet should have 75-125%

Assay• Assay is performed in finished form to

know the amount or concentration of active ingredients present in tablets

• It include HPLC, spectroscopy, chemical tests etc

Test Method STAGE-1

• Weigh about 20 tablets and crush them• To aliquot add 30ml (0.5N) NAOH

• Titrate the mixture with 0.5N HCl

• Use phenol red as indicator

• The point at which red color turns to yellow indicates the end point and the amount of HCl used is noted

STAGE-2

• Repeat the titration with blank solution of 30ml (0.5N) NaOH

• Calculate the difference of HCl consumed in both titrations.

• NOTE: Each ml of 0.5N NaOH is equivalent to 0.04502gm or 45mg of active ingredient

Formulae• Weight of 1 tablet = Total weight of tablet number of tablets

• Aliquot = Total weight of 1 tablet Active (claimed)

• %age purity = volume consumed x average weight of tablets x factor x100 active (labelled claimed) x aliquot

Dissolution• The release of drug from the tablet into

solution per unit time under standardize condition is called dissolution test.

Dissolution Apparatus1. Rotating basket method APPARATUS-I

2. Paddle method APPARATUS-II

3. Reciprocating cylinder method APPARATUS-III

4. Flow through cell method APPARATUS-IV

5. Paddle over disk method APPARATUS-V

6. Cylinder method APPARATUS-VI

7. Reciprocating disk method APPARATUS-VII

1:Rotating basket method APPARATUS-I

• The apparatus consists of a cylindrical basket held by a motor shaft

• The basket holds the sample and rotates in a round flask containing the dissolution medium

• The entire flask is immersed in a constant temperature bath set at 37°C

• The rotating speed is 100 rpm

2: Paddle method APPARATUS-II

• The apparatus consists of a special, coated paddle that minimizes the turbulence due to stirring

• The paddle is attached vertically to a variable speed motor that rotates at controlled speed

• The apparatus is housed in constant temperature water bath maintained at 37°C

• Rotating speed is 50 rpm for solid dosage forms

Paddle

3: Reciprocating cylinder method APPARATUS-III

• The apparatus consists of a set of cylindrical, flat bottomed glass vessels

• Temperature maintained at 37°C• Used for dissolution testing of extended

released products

4: Flow through cell method APPARATUS-IV

• The apparatus consists of a reservoir for dissolution medium and a pump that forces dissolution medium through cell holding the test sample

• Flow rate ranges from 4 to 16ml/min

• Temperature maintained at 37°C

5: Paddle over disk method APPARATUS-V

• The apparatus consists of a sample holder or disk assembly that holds the product

• Temperature maintained at 32°C

6: Cylinder method APPARATUS-VI

• It is modified basket method

• In place of basket, a stainless steel cylinder is used to hold the sample

• Temperature maintained at 32°C

7:Reciprocating disk method APPARATUS-VII

• A motor drive assembly is used to reciprocate the system vertically and sample is placed on disk shaped holders

• Temperature maintained at 32°C

Test method• Total tablets taken = 24 • S1 : 6 tablets taken • Acceptable: If all of the tablets are not less than

(NLT) the monograph tolerance limit (Q)= ± 5%. • If S1 fails S2 : Another 6 tables are taken • Acceptable : If average of 12 tablets is ≥ Q &

no tablet is less than Q-15% • If S2 fails S3 : 12 tablets taken • Acceptable : No tablet less than Q & not more

than 2 tablets = Q-15%.• USP limit for dissolution : NLT 75% of tablet

dissolve in 45 min.

Quality Control Tests of CAPSULES

Quality Control Quality Control TestsTests

Of CAPSULESOf CAPSULES

1: 1: DisintegrationDisintegration testtest2: Uniformity of 2: Uniformity of

WeightWeight

Disintegration of Capsules

• The disintegration of capsules is different from those of tablets because the determination of end point is difficult owing to the adhesive nature of shell.

• The shell pieces after disintegration may agglomerate forming large mass of gelatin taking more time to dissolve and may adhere to the mesh thus, blocking the holes.

Test method• Place one capsule in each of the tubes of the

basket with water or any other specified medium maintained at 37C.

• Attach a removable wire cloth with a plain square weave of 1.8-2.2 mm of mesh aperture and a wire diameter of 0.60-0.655 mm to the surface of upper rack of the basket assembly.

• Observe the capsules for a time limit • At the end of prescribed time, all of the

capsules must have been disintegrated excluding the fragments from the capsule shell.

• If 1 or 2 capsules fail, the test should be repeated on additional of 12 capsules.

• Then, not fewer than 16 of the total 18 capsules tested should disintegrate completely.

Types of Capsule

• Hard Gelatin Capsule

• Soft Gelatin Capsule

Test Method A: For Hard Gelatin Capsule

• Take 20 capsules and weigh individually

• Empty the capsules and weigh their shells (made up of gelatin)

• Take the differences of these two weights

• Differences between the weights represents weight of the contents

• Calculate the average weight of the contents of 20 tablets

• The weight of the contents of each capsule does not deviate from the average weight by a greater percentage than shown in column A

• For two capsules, the weight of the contents may deviate by not more than the percentage shown in column B

B A

15% 7.5%More than 0.120 g

20% 10%0.120 g or less

Percentage Deviation Average

Weight

Weight variation tolerances for capsules

Test Method B: For Soft Gelatin Capsule

• Take 20 capsules and weigh individually • Weigh a capsule, open it without loss of

shell material• Express as much of the contents as

possible• Wash the shell with solvent ether, reject

the washings, allow the shell to stand until ether is completely evaporated and odour of ether is no longer perceptible

• Then weigh the empty shell

• Calculate differences between weigh of each capsule and that of empty shell

• The differences between weights represents the weight of the contents

• Calculate the average of the weight of the contents of 20 capsules

• the weight of the contents of each capsule does not differ from the average weight by more than 7.5%

• Except that for one capsule the weight of the contents may differ by not more than 15%