Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Düsseldorf, Germany.
Eur J Pharm Biopharm. 2013 Nov;85(3 Pt B):1191-9. doi: 10.1016/j.ejpb.2013.04.006. Epub 2013 Apr 28.
Hot-melt extrusion is gaining importance for the production of amorphous solid solutions; in parallel, predictive tools for estimating drug solubility in polymers are increasingly demanded. The Hansen solubility parameter (SP) approach is well acknowledged for its predictive power of the miscibility of liquids as well as the solubility of some amorphous solids in liquid solvents. By solely using the molecular structure, group contribution (GC) methods allow the calculation of Hansen SPs. The GC parameter sets available were derived from liquids and polymers which conflicts with the object of prediction, the solubility of solid drugs. The present study takes a step from the liquid based SPs toward their application to solid solutes. On the basis of published experimental Hansen SPs of solid drugs and excipients only, a new GC parameter set was developed. In comparison with established parameter sets by van Krevelen/Hoftyzer, Beerbower/Hansen, Breitkreutz and Stefanis/Panayiotou, the new GC parameter set provides the highest overall predictive power for solubility experiments (correlation coefficient r = -0.87 to -0.91) as well as for literature data on melt extrudates and casted films (r = -0.78 to -0.96).
热熔挤出技术在制备无定形固体溶液方面的重要性日益增加；与此同时，人们对用于预测药物在聚合物中溶解度的预测工具的需求也在不断增加。Hansen 溶解度参数（SP）方法因其对液体混溶性以及某些无定形固体在液体溶剂中的溶解度的预测能力而得到广泛认可。仅使用分子结构，基团贡献（GC）方法就可以计算出 Hansen SPs。现有的 GC 参数集是从液体和聚合物中推导出来的，这与预测对象（固体药物的溶解度）相冲突。本研究从基于液体的 SPs 出发，将其应用于固体溶质。本研究仅基于已发表的固体药物和赋形剂的实验 Hansen SPs，开发了一个新的 GC 参数集。与 van Krevelen/Hoftyzer、Beerbower/Hansen、Breitkreutz 和 Stefanis/Panayiotou 等已建立的参数集相比，新的 GC 参数集对溶解度实验（相关系数 r = -0.87 至 -0.91）以及熔融挤出物和浇铸膜的文献数据（r = -0.78 至 -0.96）具有最高的整体预测能力。
