Comparative Study of Different Methods for the Prediction of Drug鈥揚olymer Solubility

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• 作者：Matthias Manne Knopp ; Lidia Tajber ; Yiwei Tian ; Niels Erik Olesen ; David S. Jones ; Agnieszka Kozyra ; Korbinian L枚bmann ; Krzysztof Paluch ; Claire Marie Brennan ; Ren茅 Holm ; Anne Marie Healy ; Gavin P. Andrews ; Thomas Rades
• 刊名：Molecular Pharmaceutics
• 出版年：2015
• 出版时间：September 8, 2015
• 年：2015
• 卷：12
• 期：9
• 页码：3408-3419
• 全文大小：425K
• ISSN：1543-8392

文摘

In this study, a comparison of different methods to predict drug鈥損olymer solubility was carried out on binary systems consisting of five model drugs (paracetamol, chloramphenicol, celecoxib, indomethacin, and felodipine) and polyvinylpyrrolidone/vinyl acetate copolymers (PVP/VA) of different monomer weight ratios. The drug鈥損olymer solubility at 25 掳C was predicted using the Flory鈥揌uggins model, from data obtained at elevated temperature using thermal analysis methods based on the recrystallization of a supersaturated amorphous solid dispersion and two variations of the melting point depression method. These predictions were compared with the solubility in the low molecular weight liquid analogues of the PVP/VA copolymer (N-vinylpyrrolidone and vinyl acetate). The predicted solubilities at 25 掳C varied considerably depending on the method used. However, the three thermal analysis methods ranked the predicted solubilities in the same order, except for the felodipine鈥揚VP system. Furthermore, the magnitude of the predicted solubilities from the recrystallization method and melting point depression method correlated well with the estimates based on the solubility in the liquid analogues, which suggests that this method can be used as an initial screening tool if a liquid analogue is available. The learnings of this important comparative study provided general guidance for the selection of the most suitable method(s) for the screening of drug鈥損olymer solubility.