Prudic Anke, Ji Yuanhui, Sadowski Gabriele
Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, TU Dortmund , Emil-Figge-Str. 70, D-44227 Dortmund, Germany.
Mol Pharm. 2014 Jul 7;11(7):2294-304. doi: 10.1021/mp400729x. Epub 2014 May 28.
To improve the bioavailability of poorly soluble active pharmaceutical ingredients (APIs), these materials are often integrated into a polymer matrix that acts as a carrier. The resulting mixture is called a solid dispersion. In this work, the phase behaviors of solid dispersions were investigated as a function of the API as well as of the type and molecular weight of the carrier polymer. Specifically, the solubility of artemisinin and indomethacin was measured in different poly(ethylene glycol)s (PEG 400, PEG 6000, and PEG 35000). The measured solubility data and the solubility of sulfonamides in poly(vinylpyrrolidone) (PVP) K10 and PEG 35000 were modeled using the perturbed-chain statistical associating fluid theory (PC-SAFT). The results show that PC-SAFT predictions are in a good accordance with the experimental data, and PC-SAFT can be used to predict the whole phase diagram of an API/polymer solid dispersion as a function of the kind of API and polymer and of the polymer's molecular weight. This remarkably simplifies the screening process for suitable API/polymer combinations.
为提高难溶性活性药物成分（API）的生物利用度，这些物质通常会被整合到作为载体的聚合物基质中。所得混合物称为固体分散体。在这项工作中，研究了固体分散体的相行为与API以及载体聚合物的类型和分子量之间的关系。具体而言，测定了青蒿素和吲哚美辛在不同聚乙二醇（PEG 400、PEG 6000和PEG 35000）中的溶解度。使用扰动链统计缔合流体理论（PC-SAFT）对测得的溶解度数据以及磺胺类药物在聚乙烯吡咯烷酮（PVP）K10和PEG 35000中的溶解度进行了建模。结果表明，PC-SAFT预测与实验数据吻合良好，并且PC-SAFT可用于预测API/聚合物固体分散体的整个相图，该相图是API和聚合物种类以及聚合物分子量的函数。这显著简化了合适的API/聚合物组合的筛选过程。
