کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2503464 1557426 2011 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Chemical and in vitro enzymatic stability of newly synthesized celecoxib lipophilic and hydrophilic amides
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی علوم دارویی
پیش نمایش صفحه اول مقاله
Chemical and in vitro enzymatic stability of newly synthesized celecoxib lipophilic and hydrophilic amides
چکیده انگلیسی

Five celecoxib (CXB) acylamide sodium salts, MP-CXB, Cy-CXB, Bz-CXB, CBz-CXB and FBz-CXB were synthesized and characterized. Two simple, fast and validated RP-HPLC methods were developed for simultaneous quantitative determination of the amides and celecoxib in aqueous and biological samples and LOD and LOQ were ≤13.6 and ≤40 ng/mL, respectively. The solubility and log Papp of the amides, in relevant media, were determined. The chemical hydrolysis, at 60, 70 and 80 °C, of MP-CXB was studied at GIT-relevant pH (1.2, 6.8 and 7.4) and of CY-CXB was studied at skin relative pH (5.4 and 7.4). Significant hydrolysis was observed for MP-CXB at pH 1.2 only with half-lives 28.28, 11.64 and 3.53 h at 60, 70 and 80 °C, respectively, with extrapolated half-lives of 2060 and 443 h at 25 and 37 °C, respectively. The hydrolysis of all amides was studied in rat live homogenate and only Cy-CXB was hydrolyzed with half-life of 3.79 h. The hydrolysis of MP-CXB and Cy-CXB was studied in human plasma and neither was hydrolyzed. It is finally suggested that hydrophobic interactions plays a role in the binding of susceptible acylamides to the hepatic hydrolyzing enzyme since only amides with saturated hydrocarbon chains underwent hydrolysis.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Pharmaceutics - Volume 416, Issue 1, 15 September 2011, Pages 85–96
نویسندگان
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