کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5819238 1557354 2014 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Solubility of crystalline organic compounds in high and low molecular weight amorphous matrices above and below the glass transition by zero enthalpy extrapolation
ترجمه فارسی عنوان
حلالیت ترکیبات آلی کریستالی در ماتریسهای آمورف با وزن مولکولی بالا و پایین در زیر شیشه انتقال از طریق استخراج آنتالپی صفر
کلمات کلیدی
انحلال پذیری، آمورف پلیمر دارو، امدادرسانی، تجزیه و تحلیل حرارتی،
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی علوم دارویی
چکیده انگلیسی

Pharmaceutical applications which require knowledge of the solubility of a crystalline compound in an amorphous matrix are abundant in the literature. Several methods that allow the determination of such data have been reported, but so far have only been applicable to amorphous polymers above the glass transition of the resulting composites. The current work presents, for the first time, a reliable method for the determination of the solubility of crystalline pharmaceutical compounds in high and low molecular weight amorphous matrices at the glass transition and at room temperature (i.e. below the glass transition temperature), respectively.The solubilities of mannitol and indomethacin in polyvinyl pyrrolidone (PVP) K15 and PVP K25, respectively were measured at different temperatures. Mixtures of undissolved crystalline solute and saturated amorphous phase were obtained by annealing at a given temperature. The solubility at this temperature was then obtained by measuring the melting enthalpy of the crystalline phase, plotting it as a function of composition and extrapolating to zero enthalpy. This new method yielded results in accordance with the predictions reported in the literature.The method was also adapted for the measurement of the solubility of crystalline low molecular weight excipients in amorphous active pharmaceutical ingredients (APIs). The solubility of mannitol, glutaric acid and adipic acid in both indomethacin and sulfadimidine was experimentally determined and successfully compared with the difference between their respective calculated Hildebrand solubility parameters. As expected from the calculations, the dicarboxylic acids exhibited a high solubility in both amorphous indomethacin and sulfadimidine, whereas mannitol was almost insoluble in the same amorphous phases at room temperature.This work constitutes the first report of the methodology for determining an experimentally measured solubility for a low molecular weight crystalline solute in a low molecular weight amorphous matrix.

157

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Pharmaceutics - Volume 472, Issues 1–2, 10 September 2014, Pages 241-247
نویسندگان
, , , ,