Yes / 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. / The Irish Research Council and Eli Lilly S.A. through an Irish Research Council Enterprise Partnership Scholarship for C.M.B., in part by The Royal Society in the form of Industrial Fellowship awarded to G.A., and in part by a research grant from Science Foundation Ireland (SFI) under Grant Number SFI/12/RC/2275 (for A.M.H., L.T., K.P., and A.K.).
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/14340 |
| Date | 27 July 2015 |
| Creators | 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., Healy, A.M., Andrews, G.P., Rades, T. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, Accepted manuscript |
| Rights | 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, Unspecified |
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