Drug content uniformity test

TABLET C.dat Section 4.18 Simulated drug content uniformity measurements 10 different means, starting from 46 mg, with two samples of 10 tablets each at every weight. N = 10, M = 20. To be used with HUBER, HISTO, but also CORREL to test for spurious correlations in table of random numbers and with MSD to test for conformance with limits. 

Sandell, D., Diener, M., Vukovinsky, K., Hofer, J., and Pazdan, J. (2006), Development of a content uniformity test suitable for large sample sizes, Drug. Info. J., 40, 337. 

Content uniformity testing is not a requirement for drug substance Bl, hence no information is available about the weight of the active ingredient in individual dosage units. With so much emphasis today on demonstrating adequate control over this variable, a one-time study run concurrently with the next production should be considered. Kieffer and Torbeck suggest two statistical... 

Chang, R-K. Shukla, J. Buehler, J. An evaluation of a unit-dose compacting sample thief and a discussion of content uniformity testing and blend vahdation issues. Drug Dev. Ind. Pharm. 1996, 22 (9 10), 1031-1035. 

A Zymate II Pye system for automated analysis by the Zymark Corporation (USA) with on-line HPLC has been set up and used for content uniformity tests and assays, including process validation, for a variety of drug products in our QC laboratory since January 1992. The robotic system automatically performs the following operations preparation of sample and reference standard solutions, injection into HPLC, HPLC analyses, and generation of reports. 

Figure 6.4. Example of an HPLC assay for potency (% label claim) of a drug product using reversed-phase ion pair chromatography. The same method is used for content uniformity testing.

Pharmaceutical Impurities in synthetic drugs Stability tests of synthetic drugs Content uniformity Pharmacokinetic studies and drug monitoring Assay Enantiomeric purity... 

Initial Situation An experimental granulation technique is to be evaluated a sample of tablets of the hrst trial run is sent to the analytical laboratory for the standard batch analysis prescribed for this kind of product, including content uniformity (homogeneity of the drug substance on a tablet-to-tablet basis, see USP Section (905)" ), tablet dissolution, friability (abrassion resistance), hardness, and weight. The last two tests require little time and were therefore done first. (Note Hardness data is either given in [kg-force] or [N], with 1 kg = 9.81 Newton). 

Traditionally, apart from tests such as those for appearance and weight, most tests used for the evaluation of final product are destructive in nature. Thus, for determination of such important attributes as potency or content uniformity the present conventional approach is to test a small sample of product, which hopefully is representative of the batch. Clearly it would be highly desirable if such attributes could be measured on every unit or a more representative number of units of product. Use of near-infrared offers this possibility for many if not all drugs. 

Studies involving instrumented compaction equipment can be extremely useful in the development of dosage forms, especially when the amount of drug substance is limited in quantity. Marshall has described a program in which dynamic studies of powder compaction can be used at all stages of the development process to acquire formulation information [63]. The initial experiments include a determination of the intrinsic compactability of the compound. In subsequent work, simple tablets are prepared, and tested for dissolution, potency, and content uniformity. Through studies of the compaction mechanism, it becomes possible to deduce means to improve the formulation under study. 

Several in vitro tests are currently employed to assure drug product quality. These include purity, potency, assay, content uniformity, and dissolution specifications. For a pharmaceutical product to be consistently effective, it must meet all of its quality test criteria. When used as a QC test, the in vitro dissolution test provides information for marketing authorization. The dissolution test forms the basis for setting specifications (test, methodology, acceptance criteria) to allow batch release into the market place. Dissolution tests also provides a useful check on a number of physical characteristics, including particle size distribution, crystal form, etc., which may be influenced by the manufacturing procedure. In vitro dissolution tests and QC specifications should be based on the in vitro performance of the test batches used in in vivo studies or on suitable compendial specifications. For conventional-release products, a single-point dissolution... 

Various dry powder attributes are assessed at release and on stability. These include physieal eharaeteristies sueh as appearance, content uniformity, delivered dose uniformity, and partiele size distribution. Chemieal attributes that may be assessed include drug eontent, purity, and identity, as well as the water content. Dry powders may also undergo mieroseopie evaluation for foreign particulate matter, unusual agglomeration, and partiele size. Mierobial limits should also be examined, including the total aerobie, yeast, and mold eounts. The presence of specific pathogens should be ruled out. The dry powders may be dissolved to test for pH. 

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