| Title | Characterization of polymorph transformations that decrease the stability of tablets containing the WHO essential drug mebendazole. | | Author(s) | Brits M, Liebenberg W, de Villiers MM | | Institution | Research Institute for Industrial Pharmacy and CENQAM, North-West University, Potchefstroom 2520, South Africa. | | Source | J Pharm Sci 2009 Aug 18. | | 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. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19691117 |
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