TY - JOUR
T1 - Comparative Study of Different Methods for the Prediction of Drug-Polymer Solubility
AU - Knopp, Matthias Manne
AU - Tajber, Lidia
AU - Tian, Yiwei
AU - Olesen, Niels Erik
AU - Jones, David S
AU - Kozyra, Agnieszka
AU - Löbmann, Korbinian
AU - Paluch, Krzysztof
AU - Brennan, Claire Marie
AU - Holm, René
AU - Healy, Anne Marie
AU - Andrews, Gavin P
AU - Rades, Thomas
PY - 2015/9/8
Y1 - 2015/9/8
N2 - 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 °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 °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 learnings of this important comparative study provided general guidance for the selection of the most suitable method(s) for the screening of drug-polymer solubility.
AB - 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 °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 °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 learnings of this important comparative study provided general guidance for the selection of the most suitable method(s) for the screening of drug-polymer solubility.
U2 - 10.1021/acs.molpharmaceut.5b00423
DO - 10.1021/acs.molpharmaceut.5b00423
M3 - Journal article
C2 - 26214347
VL - 12
SP - 3408
EP - 3419
JO - Molecular Pharmaceutics
JF - Molecular Pharmaceutics
SN - 1543-8384
IS - 9
ER -