ASSESSMENT OF PHARMACEUTICAL QUALITY CONTROL AND EQUIVALENCE OF VARIOUS BRANDS OF AMLODIPINE BESYLATE (5 MG) TABLETS AVAILABLE IN THE PAKISTANI MARKET UNDER BIOWAIVER CONDITIONS

摘要

Objective: The study objective was to assess the quality control tests of Amlodipine Besylate generics to assure pharmaceutical and therapeutic equivalence. Method: Six different brands of Amlodipine Besylate tablets (5 mg tablets), collected from different retail pharmacies in the local market of Pakistan, were characterized through physical and chemical parameters such as, weight variation, hardness, thickness, length, breadth, friability, disintegration, dissolution and assay. The chemical assay of the drug was carried out using a validated UV spectrophotometric method. The dissolution profiles of Amlodipine Besylate tablets under biowaiver condition were evaluated in four different media (distill water, buffer pH 1.2, buffer pH 4.5 and buffer 6.8) using US Pharmacopoeia dissolution apparatus II. Among them dissolution either single point or multiple point including release profile comparison is the most important tool. Results: Quality control tests were satisfactory and within the limits for all Amlodipine Besylate brands. The results obtained for disintegration test, assay, hardness and friability were less than 15 minutes, 98.96-100.76 %, 1.53-8.77 kg/cm2 and less than 1% respectively. The physico-chemical characteristics of the five generic brands tested were comparable with the innovator brand. They were all within the BP limits as specified for immediate release dosage forms; these assure pharmaceutical equivalence of generics tested with the innovator. The evaluated drugs were "very rapidly dissolving" because the active pharmaceutical ingredient release at time point 15 min was more than 85% so no statistical treatment is required hence are considered to be in- vitro equivalent without in -vivo evaluation. The percent relative standard deviation (% RSD) for all time points fulfills all requirements (≤20% for 15 min, ≤10% for other time points), so results are valid. Under the biowaiver conditions, all the generics are interchangeable with the innovator; they are therapeutically equivalent. The generic substitutions for the innovator are appropriate despite the high price differential. Conclusion: Product quality is the key issue for selection between generics, but how quality is assessed by pharmacists or other health practitioners is not very clear. Price differential between generics does not necessarily mean poor quality for the cheaper brand. It is obvious from the study that all brands of Amlodipine Besylate tablets are showing satisfactory results for the tests employed and are pharmaceutical equivalent, hence, so as to have cost effective therapy, cheaper brands should be prescribed / suggested by the doctors / pharmacists. In order to make objective decision about generic product selection, pharmacists and other health practitioners need adequate information on suitability of generic for substitution which should be provided by national regulatory bodies after pharmaceutical quality control evaluation of various brands of the drugs available in the market