Polymorphic Transformation of Antibiotic Clarithromycin Under Acidic Condition

Abstract Clarithromycin (CAM) is a 14-membered semisynthetic macrolide antibiotic used to treat the infection of various bacteria including Helicobacter pylori . The polymorphic transformation of CAM form II crystals under acidic conditions is, however, still unclear, and was investigated using X-ray powder diffraction method. Gel of CAM, which was immediately formed by mixing form II crystals with the hydrochloric acid solution, transformed at first to unstable form A crystals and then to form B crystals. Both forms A and B crystals are hydrochloride salts. Analyses using Hancock–Sharp equation revealed that the mechanism of form B formation was three-dimensional growth of nuclei. The rate constant of the transformation indicated that the times for 95% of form A transforming to form B at 37°C are 0.69, 1.90, and 3.79 h at pH 1.5, 2.5, and 3.4, respectively. These suggest that the transformation from form II to form B via gel and form A could occur on the surface of form II formulation of prolonged gastric residence time, in the case that the pH in stomach stays low.was fitted to the ratio.