کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2486067 1114374 2010 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Solubility advantage of amorphous pharmaceuticals: I. A thermodynamic analysis
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Solubility advantage of amorphous pharmaceuticals: I. A thermodynamic analysis
چکیده انگلیسی
In recent years there has been growing interest in advancing amorphous pharmaceuticals as an approach for achieving adequate solubility. Due to difficulties in the experimental measurement of solubility, a reliable estimate of the solubility enhancement ratio of an amorphous form of a drug relative to its crystalline counterpart would be highly useful. We have developed a rigorous thermodynamic approach to estimate enhancement in solubility that can be achieved by conversion of a crystalline form to the amorphous form. We rigorously treat the three factors that contribute to differences in solubility between amorphous and crystalline forms. First, we calculate the free energy difference between amorphous and crystalline forms from thermal properties measured by modulated differential scanning calorimetry (MDSC). Secondly, since an amorphous solute can absorb significant amounts of water, which reduces its activity and solubility, a correction is made using water sorption isotherm data and the Gibbs-Duhem equation. Next, a correction is made for differences in the degree of ionization due to differences in solubilities of the two forms. Utilizing this approach the theoretically estimated solubility enhancement ratio of 7.0 for indomethacin (amorphous/γ‐crystal) was found to be in close agreement with the experimentally determined ratio of 4.9. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1254-1264, 2010
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 99, Issue 3, March 2010, Pages 1254-1264
نویسندگان
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