کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2486058 1114374 2010 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Characterization of polymorph transformations that decrease the stability of tablets containing the WHO essential drug mebendazole
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Characterization of polymorph transformations that decrease the stability of tablets containing the WHO essential drug mebendazole
چکیده انگلیسی
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. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1138-1151, 2010
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 99, Issue 3, March 2010, Pages 1138-1151
نویسندگان
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