Department of Pharmacy, University of Tirana, Street of Dibra, Tirana, Albania.
J Pharm Sci. 2009 Nov;98(11):4216-28. doi: 10.1002/jps.21734.
The present work aims at the application of several methods to explain differences in the physical interaction of some aryl propionic acid derivatives (ibuprofen [IBP], ketoprofen [KET], flurbiprofen [FLU], naproxen [NAP], fenbufen [FEN]) with poly(vinylpyrrolidone) (PVP) K30, stored together at 298 +/- 0.5 K and 22% RH. X-ray powder diffractometry and (13)C-solid state NMR demonstrated that IBP was able to strongly interact with the polymer, while weak interaction was observed for KET, FLU, NAP, and the least for FEN. The interaction of comelted drug and PVP was studied by differential scanning calorimetry by applying the Gordon-Taylor equation, which revealed that small molar drug volumes may favour the drug diffusion through the PVP amorphous chains increasing the polymer free volume and decreasing the mixture T(g). The molecular docking study revealed that intermolecular energy is mainly due to the contribution of van der Waals energy component, causing the differences among the drugs, and is related to the drug-PVP surface contact area in the complex formed. Solid-state kinetic study demonstrated that IBP molecules are involved in a three-dimensional diffusion mechanism within the polymer favoured by its low molar volume that reduces molecular hindrance, and by the weakness of its crystal lattice, which facilitates crystallinity loss and stabilisation of the amorphous phase.
本工作旨在应用多种方法来解释几种芳基丙酸衍生物（布洛芬[IBP]、酮洛芬[KET]、氟比洛芬[FLU]、萘普生[NAP]、芬布芬[FEN]）与聚维酮（PVP）K30 在 298 ± 0.5 K 和 22% RH 下共同储存时物理相互作用的差异。X 射线粉末衍射和（13）C 固态 NMR 表明，IBP 能够与聚合物强烈相互作用，而 KET、FLU、NAP 则表现出较弱的相互作用，FEN 的相互作用最弱。通过应用 Gordon-Taylor 方程的差示扫描量热法研究了共熔融药物和 PVP 的相互作用，结果表明，小摩尔药物体积可能有利于药物通过 PVP 无定形链扩散，增加聚合物自由体积并降低混合物 T(g)。分子对接研究表明，分子间能量主要归因于范德华能量成分的贡献，导致药物之间的差异，并与形成的复合物中药物-PVP 表面接触面积有关。固态动力学研究表明，IBP 分子在聚合物中参与了三维扩散机制，其低摩尔体积降低了分子阻碍，晶格较弱，有利于结晶度损失和非晶相的稳定。
