Comparative dissolution and polymorphism study of clopidogrel bisulfate tablets available in Argentine

Abstract

Clopidogrel bisulfate (CLP) is an antiplatelet agent which exists in several solid forms. This study aimed to survey the dissolution performance of eight 75 mg CLP products available in Argentine, including the innovator brand (Plavix ® ) and the solid form of CLP in tablets. Dissolution behavior was evaluated by the United States Pharmacopeia (USP) 39 method (paddle, pH 2.0). The polymorphic state of CLP was investigated using powder X-ray diffraction (PXRD). The release profiles were compared using the similarity factor f2, bootstrap-based f2, dissolution efficiency (DE), medium dissolution time (MDT), and several kinetic models. All products met the USP specification at 30 minutes but their release characteristics varied widely. Statistical comparison of profiles indicated that only two products were found to be similar (p > 0.05) to Plavix ® in terms of DE and MDT values. Kinetically, Plavix ® and two products are fit the Weibull model, although they differed in model parameters. PXRD revealed that six products and Plavix ® contained CLP form II and one contained CLP form I. The USP method was found to be convenient for the dissolution testing of CLP products, revealing differences in rate and extent of dissolution, which could raise questions about the interchangeability of the evaluated products.