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Comparative study of different methods for the prediction of drug-polymer solubility
Knopp, M.M. Tajber, L. Tian, Y. Olesen, N.E. Jones, D.S. Kozyra, A. Lobmann, K. Paluch, Krzysztof J. Brennan, C.M. Holm, R.
Knopp, M.M.
Tajber, L.
Tian, Y.
Olesen, N.E.
Jones, D.S.
Kozyra, A.
Lobmann, K.
Paluch, Krzysztof J.
Brennan, C.M.
Holm, R.
Publication Date
2015-07
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This document is the Accepted Manuscript version of a Published Work
that appeared in final form in Molecular Pharmaceutics, copyright © 2015 American Chemical
Society after peer review and technical editing by the publisher. To access the final edited and
published work see http://dx.doi.org/10.1021/acs.molpharmaceut.5b00423
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openAccess
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2015-07-27
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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.
Version
Accepted manuscript
Citation
Knopp MM, Tajber L, Tian Y et al (2015) Comparative study of different methods for the
prediction of drug-polymer solubility. Molecular Pharmaceutics. 12(9): 3408-3419.
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Article