REVIEW:- INDUSTRIAL PROCESS VALIDATION OF TABLET DOSAGE FORM
Coating solution: The concentration and viscosity of the coating solution will need to be determined. The solution will need to be sufficiently diluted in order to spray the material on the tablets. The concentration of the coating solution will also determine the amount and volume of solution to be applied to the tablets. The stability of the coating solution should be investigated to establish its shelf life.
Coating weight: A minimum and maximum coating weight should be established for the tablet. Sufficient coating material should be applied to the tablets to provide a uniform appearance; however, it should not be great enough to cause fill-in of the intagliation.
Residual solvent level: If solvents are used for tablet coating, the residual solvent level will need to be determined.
Appearance testing of the tablets is critical during the coating operation. Items to look for include the following:
1. Cracking or peeling of the coating.
2. Intagliation fill-in.
3. Surface roughness.
4. Color uniformity.
Coating efficiency should be determined for the coating operation. The efficiency will determine the amount of coating solution overage that may be required.
1. Moisture content of “dried granulation”: Loss on drying (LOD) can be used to determine whether or not the granulation solvent has been removed to a sufficient level during the drying operation (usually less than 2% moisture).
2. Granulation particle size distribution: An extremely important parameter that can affect tablet compressibility, hardness, thickness, disintegration, dissolution, weight variation, and content uniformity. This parameter, which can be done by sieve analysis, should be monitored throughout the tablet validation process.
3. Blend uniformity: Samples of the blend are taken and analyzed to ensure that the drug is uniformly dispersed throughout the tablet/capsule blend. The proper blend time must be established so that the blend is not under- or over mixed. The sampling technique is critical for this test to be valid.
4. Individual tablet: the weight of individual tablets is determined throughout compression/encapsulation to ensure that the material is flowing properly and the equipment is working consistently. The individual weight should be within 5% of the nominal weight. Weight fluctuations or frequent machine adjustments suggest that the formulation/process (e.g. poor granulation flow) is not optimized and/or that the equipment may need maintenance.
5. Tablet hardness: Tablet hardness is determined periodically throughout the batch to ensure that the tablets are robust enough for coating, packing, and shipping and not too hard to affect dissolution.
6. Tablet thickness: Tablet thickness is also determined periodically throughout the batch and is indirectly related to the hardness. It is another indication of whether or not the formulation has proper flow and compression properties.
7. Disintegration: Disintegration is determined during the manufacture as a predictor of tablet performance
B. Finished Product Tests
1. Appearance: The tablets should be examined for such problems as tablet mottling, picking of the monogram, tablet filming, and capping of the tablets. If the tablets are colored, the color quality needs to be examined.
2. Assay: This test will determine whether or not the product contains the labeled amount of drug.
3. Content uniformity: Samples are taken across the batch profile (beginning, middle, and end) and analyzed to ensure that the dosage forms comply with compendial standards (}15% of the labeled amount) or more stringent internal limits. It will indicate whether there is demixing during the manufacturing operation (i.e., segregation during flow of granulation from a storage bin).
4. Tablet hardness: A critical parameter for dosage form handling and performance.
5. Tablet friability: Friability is an important characteristic on the tablets’ ability to withstand chipping, cracking, or “dusting” during the packaging operations and shipping.
6. Dissolution: Dissolution is important to ensure proper drug release characteristics (in vitro availability) and batch-to-batch uniformity.
Fig: - validation of existing manufacturing process.
Tablet dosage form should be integral part of the comprehensive validation program me within the industry. The total program me should begin with the validation of API so that material will remain uniform from batch to batch. The scientific information which is obtained during the preformulation stage can form the basis for the validation program me Validation of a new or existing product involves the efforts of scientists at various stages of the product development life cycle. Scientific information obtained during the preformulation stage can form the basis for a well-designed and comprehensive validation program. Continued awareness of validation requirements and a diligent application of validation principles will thus help to ensure that pharmaceutical products will be able to be developed and produced with the quality and reproducibility required from regulatory agencies across the world.
1. U.S. Food and Drug Administration. Guideline on General principles of Process Validation. Rockville, MD; May, 1987.
2. Nash RA, Watcher AH. Pharmaceutical Process Validation. 3rd Ed. New York: Marcel Dekker, INC;1990. P.159-180.
3. Mehta R.M. Processing of tablets, Pharmaceutics-1. Delhi: Vallabh prakashan; 2002.P.238-267.
4. U.S. FDA. Guideline on general principles of process validation. Guide Indus May (1987).
5. Rippie, E. G. Mixing. In: L. Lockman, H. Lieberman, I. Kanig, eds. Theory and Practice of Industrial Pharmacy. 2nd ed. Philadelphia: Lea & Febiger, pp. 486–502(1976).
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