期刊
MOLECULAR PHARMACEUTICS
卷 12, 期 9, 页码 3408-3419出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.5b00423
关键词
solubility; polymers; solid dispersion; thermal analysis; thermodynamics; calorimetry (DSC); amorphous; Flory-Huggins; melting point depression; recrystallization
资金
- Irish Research Council
- Eli Lilly SA through an Irish Research Council Enterprise Partnership Scholarship
- Royal Society
- Science Foundation Ireland (SFI) [SFI/12/RC/2275]
In this study, a comparison of different methods to predict drug-polymer 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-polymer solubility at 25 degrees C was predicted using the Flory-Huggins 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 degrees 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-PVP 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 leamings of this important comparative study provided general guidance for the selection of the most suitable method(s) for the screening of drug-polymer solubility.
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