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1Malay N. JivaniPrepared by:Malay N. JivaniM.Pharm sem 2 (Ceutics)Sub. PVcGMPIPQC Tablet

What is IPQC ?IPQC is concerned with providing accurate, specific, and definite description of procedures to be employed from the receipt of raw materials to the release of finished dosage forms.IPQC Procedures are generally quick, sipmle and rapid tests or inspection that carried out at on going manufacturing .It is a planned system to identify the materials, equipment, process, and operations.

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Why we need IPQC?To detect the errorsTo minimize the human errors.Provides accurate, specific, and definite description of the procedure to be employed.Rigidly followed.Should detect any abnormality immediately and at the same time indicate the kind of action needed to correct the problem.To enforce the flow of manufacturing and packing operations according to established routes and practice.

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Who do IPQC?Usually, the tests are carried out by production personnel. This is favourable for organizational and timely reasons, e.g. in a multi-shift operation. The personnel in production area referred to here do not have to be directly responsible to the head of production with disciplinary responsibility. On the basis of organisational instructions and process descriptions, quality control personnel may also carry out the necessary tasks.

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Where to to do IPQC?In-process controls may be carried out within the production area provided they do not carry any risk for the production.5Malay N. Jivani

In-Process Quality Control tests for TabletsHardnessFriability Thickness Disintegration Time Weight variation Content uniformity Dissolution testLeakage testing for strip and blister packaging

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HardnessIt is the load required to crush the tablet when placed on its edge. It determine the need for pressure adjustments on the tableting machine. Hardness can affect the disintegration. So if the tablet is too hard, it may not disintegrate in the required period of time. And if the tablet is too soft, it will not withstand the handling during subsequent processing such as coating or packaging. In general, if the tablet hardness is too high, we first check its disintegration before rejecting the patch. And if the disintegration is within limit, we accept the patch. If Hardness is high + disintegration is within time -- accept the batch7Malay N. Jivani

Factor effecting HardnessCompression of the tablet and compressive force. Amount of binder. (More binder more hardness) Method of granulation in preparing the tablet (wet method gives more hardness than direct method, Slugging method gives the best hardness).Limits: 5 kilograms minimum and 8 kilograms maximum.8Malay N. Jivani

Haedness testers1. Monsanto tester 2. Strong-cobb tester 3. Pfizer tester 4. Erwica tester

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FriabilityIt 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 tablets 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.10Malay N. Jivani

How it determinedFriability of a tablet can determine in laboratory by Roche friabilator. This consist of a plastic chamber that revolves at 25 rpm, dropping the tablets through a Distance of six inches in the friabilator, which is then operate for 100 revolutions. The tablets are reweighed. Compress tablet that lose less than 0.5 to 1.0 % of the Tablet weigh are consider acceptable. Friability (% loss) = W1 - W2/100W1 = Initial Weigh 20 tabletsW2 = Weigh 20 tablets after 100 rotation

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Roche friabilator

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Thickness The thickness of a tablet depends on the upper and lower punches at the moment of compression. it can be tested using vernier calipers. The range varies with +/- 5.0%. VERNIER CALIPERS

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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. The end point of the test (i.e. complete disintegration) is achieved when no tablet fragments remain on the screen.The preparation complies with the test if the time to reach thisend-point is below given limit; < 30 minutes for uncoated immediate release tablets. but varying from 2 min for nitroglycerin sublingual tablets to up to 4 hrs for buccal tabletsIf one or two tablets failed to disintegrate, repeat test on 12 additional tablets: at least 16 of the 18 (6 + 12) tested tablets should pass the test.

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The disintegration apparatus

Six tubes opened at the upper end and closed by a screen at the lowerA cylindrical disk of transparent plastic is also used if specified in monograph.15Malay N. Jivani

Content uniformity This test is done to ensure that every tablet contains the amount of drug substance intended with little variation within a batchProcedure In this test 30 tablets are randomly selected for the sample and atleast 10 of them assayed individually 9 of the 10 tablets must contain not less than 85% or more than 115 % of labeled drug content. 10th tablet may not contain less than 75% or more than 125% of labeled content.If this conditions are not meet the tablet remaining from the 30 must be assayed individually and none may fall outside 85 to 115 % .

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Weight variation The volumetric fill of the die cavity determines the weight of the compressed tablet . The weight of the tablet is the quantity of the granulation that contains the labeled amount of the therapeutic ingredient. After the tablet machine in operation the weights of the tablets are routinely checked to ensure that proper tablet weights are made. Procedure : Take 20 tablets and ,measure the individual weights of each tablets Take average weights of 20 tablets Compare the individual weight of tablets with avg weight. Not more than 2 tablets should deviate from avg weight by percent deviaton and none should deviate more than twice the percentage17Malay N. Jivani

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IP standard for weight variationSr. NoAverage wt. of tablet(mg)Max. % difference allowed184 or Less10%284- 2507.5%3More than 2505%

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Dissolution testDissolution is performed to check the percentage release from the dosage forms from the tablet. When tablet disintegrate it breaks down into small particles which offers a greater surface area to the dissolving media and drug will dissolve.

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Mainly used Dissolution apparatus(IP)Dissolution apparatus I ( Basket method)Malay N. Jivani21

Malay N. Jivani22 Dissolution apparatus II ( Basket method)

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Dissolution testing interpretation IP StandardSr.no.Quantity Stage/levelNumber of tablets testedAcceptance criteria1S16Each unit is < D* + 5 percent**2S26Average of 12 units (S1 +S2) is equal to or greater than (> )D, and no unit is less than D - 15 percent**3S312Average of 24 units (S1+S2+S3) is equal to or greater than (> )D, not more than 2 units are less than d-15 percent** and no unit is less than d-25 percent**

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Leak testing for Strips and Blister packingTake the required number of strips / blisters as mentioned in annexure . Check the quality of strips/ blisters for any damages.Tie the collected strips / blisters with a rubber band. Ensure that all strips / blisters are dipped in water and close the lid. Connect opening of the desiccator to the vacuum pump.Apply a vacuum of 300 mm of Hg and close the knob of the desiccator.Keep the vacuum for 30sec. Release the vacuum by opening the knob of the desiccator slowly and open the lid remove the strips / blisters.Wipe out the traces of water from the strips / blisters by using lint free duster .Open the pocket of strips by using scissors to remove the tablets / capsules.Open the blisters manually. Check for any traces of water inside the strips / blisters.Number of tablets or capsules, which have become wet, should not be more than 1% .

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Comparison of Specifications and ParametersTests IPBPUSPContenter uniformity98- 102 %NSNSDrug Content 90 110 %NSNSContent uniformity85 - 115 %85 - 115 %85 - 115 %

Weight uniformity