کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8514838 | 1556512 | 2016 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Long-Acting Diclofenac Ester Prodrugs for Joint Injection: Kinetics, Mechanism of Degradation, and In Vitro Release From Prodrug Suspension
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Long-Acting Diclofenac Ester Prodrugs for Joint Injection: Kinetics, Mechanism of Degradation, and In Vitro Release From Prodrug Suspension Long-Acting Diclofenac Ester Prodrugs for Joint Injection: Kinetics, Mechanism of Degradation, and In Vitro Release From Prodrug Suspension](/preview/png/8514838.png)
چکیده انگلیسی
A prodrug approach for local and sustained diclofenac action after injection into joints based on ester prodrugs having a pH-dependent solubility is presented. Inherent ester prodrug properties influencing the duration of action include their pH-dependent solubility and charge state, as well as susceptibility to undergo esterase facilitated hydrolysis. In this study, physicochemical properties and pH rate profiles of 3 diclofenac ester prodrugs differing with respect to the spacer carbon chain length between the drug and the imidazole-based promoiety were determined and a rate equation for prodrug degradation in aqueous solution in the pH range 1-10 was derived. In the pH range 6-10, the prodrugs were subject to parallel degradation to yield diclofenac and an indolinone derivative. The prodrug degradation was found to be about 6-fold faster in 80% (vol/vol) human plasma as compared to 80% (vol/vol) human synovial fluid with 2-(1-methyl-1H-imidazol-2-yl)ethyl 2-(2-(2,6 dichlorophenyl)amino)phenylacetate being the poorest substrate toward enzymatic cleavage. The conversion and release of parent diclofenac from prodrug suspensions in vitro were studied using the rotating dialysis model. The results suggest that it is possible to alter and control dissolution and reconversion behavior of the diclofenac prodrugs, thus making the prodrug approach feasible for local and sustained diclofenac action after joint injection.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 105, Issue 10, October 2016, Pages 3079-3087
Journal: Journal of Pharmaceutical Sciences - Volume 105, Issue 10, October 2016, Pages 3079-3087
نویسندگان
Nina Mertz, Susan Weng Larsen, Jesper Kristensen, Jesper Ãstergaard, Claus Larsen,