QUALITY CONTROL TESTS OF TABLETS PHYSICAL TESTS CHEMICAL TESTS 2: Tablet Thickness1: Hardness Test and 1: Content Uniformity 2: Assay Diameter 4: Disintegration 5: Weight Variation 3: Friability Test 3: Dissolution Test Test Test
Hardness It is defined as the force required to break a tablet in a diametric compression test. Tablet requires a certain amount of strength or hardness and resistance to friability to withstand mechanical shakes of handling in manufacture, packaging and shipping. Tablet Hardness Test is performed to check that the manufactured tablet is of desired hardness.
1:Strong-Cobb• The tablet is placed between two jaws that crush the tablet.• The machine measures the force applied to the tablet and detects when it fractures.
2:Stokes-Monsanto Tube like structure in which tablet is placed. Force in kg is required to break tablet. 4kg is general range
3: Eureka The breaking force is applied by a beam fastened to one end to a pivot The motor moves a weight along the beam at a constant speed and increases the force against the tablet on which the other end of the beam rests When the tablet breaks, a microswitch is activated that stops the motor An indicator fastened to the weight shows the breaking strength on scale in kilogram units
Factors Affecting Hardness Pressure applied during the compression Cohesive forces between ingredients especially binder have more cohesive forces Density
Thickness and Diameter Tablet thickness and diameter tests are also very important qc tests Very thick tablet affects packaging either in blister or plastic container The thickness for majority of tablets may vary from 2mm to 4mm The diameter of tablets may vary from 4mm to 13mm
Instruments used For diameter: Vernier Calipers For thickness: Micrometer Screw Gauge
Friability► It is the tendency of tablets to powder, chip, or fragment and this can affect the elegance appearance, consumer acceptance of the tablet, and also add to tablet’s weight variation or content uniformity problems.► Friability is a property that is related to the hardness of the tablet.► An instrument called friabilator is used to evaluate the ability of the tablet to withstand abrasion in packaging, handling, and shipping.
Friabilator► Friabilator is a round drum► It has diameter of 2.87mm and depth of 38mm► In diameter a horizontal axis is present► Friabilator is connected to timer to indicate its rotations► It is rotated in clockwise direction
Test Method► Weigh 20 tab altogether = W1► Put these tablets in the friabilator and adjust the instrument at 100 rpm (i.e. = 25 rpm for 4 min)► Weigh the 20 tablets (only the intact ones) = W2► The difference between W1 and W2 gives weight loss (i.e. Friability)► Weight loss of 1-5% is acceptable
Disintegration For most tablets , the first important step towards formation of solution is breakdown of the tablet into smaller particles or granules , this process is known as disintegration. It is the time required for the tablet to break into particles, the disintegration test is a measure only of the time required under a given set of conditions for a group of tablets to disintegrate into particles
Disintegration apparatus The apparatus consists of; Basket rack assembly A suitable vessel for the immersion liquid A thermostatic arrangement for heating the fluid between 35°C and 39°C A device for raising and lowering the basket in the immersion fluid at a constant frequency rate between 28 and 32 cpm through a distance of not less than 5cm and not more than 6cm
BASKET RACK ASSEMBLY:- It consists of; Six open ended glass tubes each 7.75cm long and having an inside diameter of approximately 21.5mm and a wall 2mm thick The tubes are held in a vertical position by two plastic plates Each tube is provided with a slotted and perforated cylindrical disk
1: Test method for Uncoated tablets Place 1 tablet in each of the 6 tubes of the basket, add a disk to each tube Use water as immersion fluid maintained at 37°C If one or two tablets from the 6 tablets fail disintegrate completely within 30min repeat the same test on another 12 tablet. (i.e. the whole test will consume 18 tablets). Not less then 16 tablets disintegrate completely within the time
if more then two tablets (from the 18) fail to disintegrate, the batch must be rejected.
2: Test method for coated tablets Place 1 tablet in each of the 6 tubes of the basket, add a disk to each tube To remove or dissolve the coat, immerse the basket in distilled water for 5min. Then add a disk to each tube and operate the apparatus using simulated gastric fluid maintained at 37°C If one or two tablets fail to disintegrate, repeat on 12 tablets.
So 16 tablets from the 18 must completely disintegrate within the time If two or more not disintegrated the batch is rejected
3: Test method for Enteric coated tablets Place 1 tablet in each of the 6 tubes of the basket, add a disk to each tube Put in distilled water for five minutes to dissolve the coat. Then operate the apparatus without the disks using simulated gastric fluid as immersion fluid maintained at for one hour. After one hour, lift the basket and observe the tablets, the tablets show no evidence of disintegration, cracking or softening
Then add disk to each tube and operate the apparatus using simulated intestinal fluid maintained at 37°C for two hours. If one or two tablets fail to disintegrate, repeat this test on another 12 tablets. So 16 tablets from 18 should completely disintegrate. If more than two fail to disintegrate the batch must be rejected.
4: Test method for Buccal tablets Place 1 tablet in each of the 6 tubes of the basket Use water as immersion fluid maintained at 37°C Operate the apparatus for 4 hours If one or two tablets fail to disintegrate, repeat this test on another 12 tablets. So 16 tablets from 18 should completely disintegrate. If more than two fail to disintegrate the batch must be rejected
5: Test method for Sublingual tablets Place 1 tablet in each of the 6 tubes of the basket Use water as immersion fluid maintained at 37°C If one or two tablets fail to disintegrate, repeat this test on another 12 tablets. So 16 tablets from 18 should completely disintegrate. If more than two fail to disintegrate the batch must be rejected
Factors Affecting Disintegration Quantity of disintegrating agent Compactness Cohesive forces between the ingredients Hardness
Weight Variation The actual weight of a tablet is determined by the diameter of the die and the weight adjustment cam on the tablet machine The weight control on the tablet machine is routinely adjusted at intervals to ensure that the specified weight is being reproduced This test is perform to ensure uniform distribution of ingredients throughout batch
Test Method Take 20 tablets Weigh individually Determine the average weight of 20 tablets Compare individual tablet weight to average weight Not more than 2 of the individual weights deviate from the average weight by more than the percentage deviation And none deviates by more than twice that percentage.
Weight variation tolerances foruncoated tablets in U.S.P XVII Average weight of Percentage Differences Tablet (mg) 130 or less 10.0 130-324 7.5 More than 324 5.0
Causes of Weight Variation1. Poor flow of granules2. Variation in size of granules due to improper sieving3. Presence of very fine granules4. Improper adjustment of machine5. Improper flow rate
Content 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 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-I2. Paddle method APPARATUS-II3. Reciprocating cylinder method APPARATUS-III4. Flow through cell method APPARATUS-IV5. Paddle over disk method APPARATUS-V6. Cylinder method APPARATUS-VI7. 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
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 2: Uniformity of1: Disintegration test Weight
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
Weight variation tolerances for capsules Average Percentage Deviation Weight A B0.120 g or less 10% 20%More than 7.5% 15%0.120 g
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%
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