title: Characterization of polymorph transformations that decrease the stability of tablets containing the WHO essential drug mebendazole.
abstract: This study investigated the influence of moisture and heat on the stability of mebendazole polymorph C in tablets. The polymorphic forms of mebendazole display significant differences in solubility and therapeutic efficacy and form C is preferred clinically due to its optimal bioavailability and reduced toxicity. An accelerated stability study of the polymorphs revealed that the Johnson-Mehl-Avrami-Erofeyev-Kolmogorov (JMAEK) model best described the kinetics of the solid-state transformation of form C to A. Rate constants obtained using this model was used to calculated half-lives and shelf lives of products stored under ICH conditions of 30 degrees C + 65% RH and 40 degrees C + 75% RH. Results showed that form C was converted to the thermodynamic stable, least soluble form A with increased temperatures and moisture, and at constant temperature and relative humidity this transformation was significantly increased when trace amounts of form A was present in the tablets. Four out of the seven products tested contained trace amounts of form A. In some tablets, the transformation to form A was so quick that it reduced the shelf life to less than 1 month. The tablet dissolution of these products was reduced to such an extent that it did not comply with USP and FDA specifications.
authors.affiliation: Research Institute for Industrial Pharmacy and CENQAM, North-West University, Potchefstroom 2520, South Africa.
authors.forename: Marius
authors.initials: M
authors.lastname: Brits
authors.forename: Wilna
authors.initials: W
authors.lastname: Liebenberg
authors.forename: Melgardt M
authors.initials: MM
authors.lastname: de Villiers
mesh_terms: D000969:Antinematodal Agents / Q000737:chemistry*; D003460:Crystallization / Q000379:methods*; D004355:Drug Stability; D007700:Kinetics; D008463:Mebendazole / Q000737:chemistry*; D011208:Powders / Q000737:chemistry; D012995:Solubility; D013607:Tablets / Q000737:chemistry*; D013696:Temperature; D014944:World Health Organization
chemical_list: D000969:Antinematodal Agents; D011208:Powders; D013607:Tablets; D008463:Mebendazole