Comparative Study of Different Methods for the Prediction of Drug-Polymer Solubility

Matthias Manne Knopp; Lidia Tajber; Yiwei Tian; Niels Erik Olesen; David S Jones; Agnieszka Kozyra; Korbinian Löbmann; Krzysztof Paluch; Claire Marie Brennan; René Holm; Anne Marie Healy; Gavin P Andrews; Thomas Rades

doi:10.1021/acs.molpharmaceut.5b00423

Comparative Study of Different Methods for the Prediction of Drug-Polymer Solubility

Matthias Manne Knopp, Lidia Tajber, Yiwei Tian, Niels Erik Olesen, David S Jones, Agnieszka Kozyra, Korbinian Löbmann, Krzysztof Paluch, Claire Marie Brennan, René Holm, Anne Marie Healy, Gavin P Andrews, Thomas Rades

Disease Systems Biology Program

67 Citations (Scopus)

Abstract

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. (Graph Presented).

Original language	English
Journal	Molecular Pharmaceutics
Volume	12
Issue number	9
Pages (from-to)	3408-19
Number of pages	12
ISSN	1543-8384
DOIs	https://doi.org/10.1021/acs.molpharmaceut.5b00423
Publication status	Published - 8 Sept 2015

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title = "Comparative Study of Different Methods for the Prediction of Drug-Polymer Solubility",

abstract = "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. (Graph Presented).",

author = "Knopp, {Matthias Manne} and Lidia Tajber and Yiwei Tian and Olesen, {Niels Erik} and Jones, {David S} and Agnieszka Kozyra and Korbinian L{\"o}bmann and Krzysztof Paluch and Brennan, {Claire Marie} and Ren{\'e} Holm and Healy, {Anne Marie} and Andrews, {Gavin P} and Thomas Rades",

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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

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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. (Graph Presented).

U2 - 10.1021/acs.molpharmaceut.5b00423

DO - 10.1021/acs.molpharmaceut.5b00423

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SP - 3408

EP - 3419

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

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ER -

Comparative Study of Different Methods for the Prediction of Drug-Polymer Solubility

Abstract

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