Kyeremateng Samuel O, Pudlas Marieke, Woehrle Gerd H
AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany.
AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany.
J Pharm Sci. 2014 Sep;103(9):2847-2858. doi: 10.1002/jps.23941. Epub 2014 Mar 13.
A novel empirical analytical approach for estimating solubility of crystalline drugs in polymers has been developed. The approach utilizes a combination of differential scanning calorimetry measurements and a reliable mathematical algorithm to construct complete solubility curve of a drug in polymer. Compared with existing methods, this novel approach reduces the required experimentation time and amount of material by approximately 80%. The predictive power and relevance of such solubility curves in development of amorphous solid dispersion (ASD) formulations are shown by applications to a number of hot-melt extrudate formulations of ibuprofen and naproxen in Soluplus. On the basis of the temperature-drug load diagrams using the solubility curves and the glass transition temperatures, physical stability of the extrudate formulations was predicted and checked by placing the formulations on real-time stability studies. An analysis of the stability samples with microscopy, thermal, and imaging techniques confirmed the predicted physical stability of the formulations. In conclusion, this study presents a fast and reliable approach for estimating solubility of crystalline drugs in polymer matrixes. This powerful approach can be applied by formulation scientists as an early and convenient tool in designing ASD formulations for maximum drug load and physical stability.
一种用于估算结晶药物在聚合物中溶解度的新型经验分析方法已被开发出来。该方法利用差示扫描量热法测量和可靠的数学算法相结合，构建药物在聚合物中的完整溶解度曲线。与现有方法相比，这种新方法将所需的实验时间和材料量减少了约80%。通过应用于布洛芬和萘普生在Soluplus中的多种热熔挤出物制剂，展示了这种溶解度曲线在无定形固体分散体（ASD）制剂开发中的预测能力和相关性。基于使用溶解度曲线和玻璃化转变温度的温度-药物负载图，通过对挤出物制剂进行实时稳定性研究来预测和检查其物理稳定性。用显微镜、热分析和成像技术对稳定性样品进行分析，证实了制剂预测的物理稳定性。总之，本研究提出了一种快速且可靠的方法来估算结晶药物在聚合物基质中的溶解度。这种强大的方法可被制剂科学家用作设计ASD制剂以实现最大药物负载和物理稳定性的早期便捷工具。
