EQUIVALENCE OF VARIOUS BRANDS OF AMLODIPINE BESYLATE (5 MG) TABLETS IN BIOWAIVER CONDITION

Background: A biowaiver based on the Biopharmaceutics Classification System (BCS) allows in vivo bioequivalence testing to be replaced by comparative in vitro dissolution for immediate-release solid oral dosage forms containing highly soluble and highly permeable drugs. Amlodipine besylate is classified as a BCS Class I drug and therefore qualifies for this approach. More than 40 Nepali manufacturers market amlodipine, but the quality and interchangeability of these products had not previously been assessed. Objective: To evaluate the pharmaceutical quality of amlodipine besylate (5 mg) tablets available in the Nepali market and to assess their equivalence with the innovator product under biowaiver conditions. Materials and Methods: Eight generic amlodipine besylate 5 mg tablet brands were randomly collected from hospital, retail and community pharmacies in Nepal and coded A to H. The innovator product (Pfizer), coded I, was obtained from India and used as the reference. Weight variation, hardness and drug content were determined, the last by a UV spectrophotometric method at 240 nm against a calibration curve prepared from standard amlodipine. In vitro dissolution was carried out on 12 tablets per brand using USP apparatus 2 at 75 rpm in 900 mL of three media (0.1 N HCl pH 1.2, acetate buffer pH 4.5 and phosphate buffer pH 6.8) at 37 ± 2 ºC, with sampling at 10, 15, 20, 30 and 45 minutes. Dissolution profiles of each generic were compared with the innovator using the difference factor (f1) and similarity factor (f2), with similarity accepted at f1 ≤ 15 and f2 ≥ 50. Results: Average tablet weights ranged from 0.11 to 0.19 g and hardness from 1.5 to 5 kg/cm2, with no marked differences between brands. Drug content ranged from 86.87 % to 124.13 %. Two of the eight generics fell outside the USP acceptance range of 90–110 %: brand G at 86.87 % and brand D at 124.13 %. At 45 minutes, all products released more than 88 % of the labelled amount in every medium, and several values exceeded 100 %. Profile comparison gave a different picture from the endpoint data. Brand B showed the closest agreement with the innovator (f2 of 72, 79 and 77 at pH 1.2, 4.5 and 6.8), followed by brand H (59, 66 and 85). Brand C failed the similarity criterion in all three media (f2 of 43, 34 and 46), and brands A and F each failed in one medium. Products that met the criteria in all three media were therefore a minority, even though nearly all products had released most of the drug by 45 minutes. Conclusion: Within the conditions of this study, all brands met the physical quality tests, but two failed the content uniformity requirement and only a small number matched the innovator dissolution profile across all three media. The findings indicate that not all amlodipine generics on the Nepali market can be assumed to be interchangeable with the innovator, and support the need for routine post-marketing quality assessment.