INVITE GmbH, Drug Delivery Innovation Center (DDiC), 51368 Leverkusen, Germany.
TU Dortmund University, Department of Biochemical and Chemical Engineering, Laboratory of Thermodynamics, Emil-Figge-Strasse 70, D-44227 Dortmund, Germany.
Mol Pharm. 2022 Jul 4;19(7):2483-2494. doi: 10.1021/acs.molpharmaceut.2c00188. Epub 2022 Jun 21.
Amorphous solid dispersions (ASDs), where an active pharmaceutical ingredient (API) is dissolved in a polymer, are a favored formulation technique to achieve sufficient bioavailability of poorly water-soluble APIs. The shelf life of such ASDs is often limited by API crystallization. Crystallization depends strongly on the storage conditions (relative humidity and temperature) and the polymer selected for generating the ASD. Determining the crystallization kinetics of ASDs under various conditions requires suitable analytical methods. In this work, two different analytical methods were compared and cross-validated: The first builds on water-sorption measurements combined with thermodynamic predictions ( 2018, 127, 183-193, DOI: 10.1016/j.toxrep.2018.11.002), whereas the second applies Raman spectroscopy. Using the two independent methods, factors influencing the crystallization kinetics of ASDs containing the API griseofulvin were investigated quantitatively. It was found that crystallization kinetics increases with increasing temperature and relative humidity. Additionally, the influence of different polymers (poly(vinylpyrrolidone--vinyl acetate) and Soluplus) on crystallization kinetics were investigated. The experimentally obtained crystallization kinetics were described using the Johnson-Mehl-Avrami-Kolmogorov model and are the basis for future shelf life predictions at desired storage conditions.
无定形固体分散体（ASD）是将活性药物成分（API）溶解在聚合物中的一种首选制剂技术，可实现水溶性差的 API 的足够生物利用度。此类 ASD 的保质期通常受 API 结晶的限制。结晶强烈依赖于储存条件（相对湿度和温度）以及用于生成 ASD 的聚合物。确定各种条件下 ASD 的结晶动力学需要合适的分析方法。在这项工作中，比较并交叉验证了两种不同的分析方法：第一种方法基于水吸附测量结合热力学预测（2018 年，127 卷，第 183-193 页，DOI：10.1016/j.toxrep.2018.11.002），而第二种方法则应用拉曼光谱。使用这两种独立的方法，定量研究了含有 API 灰黄霉素的 ASD 的结晶动力学的影响因素。结果发现，结晶动力学随温度和相对湿度的增加而增加。此外，还研究了不同聚合物（聚乙烯吡咯烷酮-醋酸乙烯酯和 Soluplus）对结晶动力学的影响。使用 Johnson-Mehl-Avrami-Kolmogorov 模型描述了实验获得的结晶动力学，这是在所需储存条件下进行未来保质期预测的基础。
