Application of biowaiver methodology for a post-marketing study of generic and brand name metronidazole tablets

Abstract

An important component of evaluation of generic medicines is assessing their therapeutic equivalence, which is done by a comparative study with an appropriate comparator, such as an in vivo bioequivalence study or an in vitro dissolution study. In vivo bioequivalence studies are cumbersome and expensive. Their need might be waived using in vitro dissolution for selected drugs. In this post marketing study, we conducted in vitro dissolution testing according to the WHO guideline for biowaiver studies comparing a generic metronidazole product available in Sri Lanka with an appropriate comparator. The results showed that both products complied with the pharmacopoeial specifications, and that the generic (test) product is similar to the comparator product, with very rapid dissolution properties. In vitro dissolution of the test product was similar to the comparator in media with pH 1.2, 4.5, and 6.8, representing gastric, duodenal, and jejunal conditions. Based on the study findings, the tested metronidazole product demonstrates in vitro equivalence to the comparator product. Similarity of the dissolution profile indicates high probability of in vivo bioequivalence of the generic product compared to the brand name product, in the absence of bioequivalence data. According to the International Pharmaceutical Federation (FIP) biowaiver monograph for metronidazole, the quality and quantity of the excipient also needs evaluation for the two products to be considered therapeutically equivalent. Therefore, if the excipient composition is available, the decision of interchangeability of the two products could be made.