Characterization of polymorph transformations that decrease the stability of tablets containing the who essential drug mebendazole
De Villiers, Melgardt M.
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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°C + 65% RH and 40°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