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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    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.
    OriginalsprogEngelsk
    TidsskriftMolecular Pharmaceutics
    Vol/bind12
    Udgave nummer9
    Sider (fra-til)3408–3419
    ISSN1543-8384
    DOI
    StatusUdgivet - 2015

    Citer dette

    Knopp, M. M., Tajber, L., Tian, Y., Olesen, N. E., Jones, D. S., Kozyra, A., ... Rades, T. (2015). Comparative Study of Different Methods for the Prediction of Drug-Polymer Solubility. Molecular Pharmaceutics, 12(9), 3408–3419. https://doi.org/10.1021/acs.molpharmaceut.5b00423
    Knopp, Matthias Manne ; Tajber, Lidia ; Tian, Yiwei ; Olesen, Niels Erik ; Jones, David S. ; Kozyra, Agnieszka ; Löbmann, Korbinian ; Paluch, Krzysztof ; Brennan, Claire Marie ; Holm, René ; Healy, Anne Marie ; Andrews, Gavin P. ; Rades, Thomas. / Comparative Study of Different Methods for the Prediction of Drug-Polymer Solubility. I: Molecular Pharmaceutics. 2015 ; Bind 12, Nr. 9. s. 3408–3419.
    @article{98bd4d211aec4c4e8bafb2baad15a420,
    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.",
    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",
    year = "2015",
    doi = "10.1021/acs.molpharmaceut.5b00423",
    language = "English",
    volume = "12",
    pages = "3408–3419",
    journal = "Molecular Pharmaceutics",
    issn = "1543-8384",
    publisher = "American Chemical Society",
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    Knopp, MM, Tajber, L, Tian, Y, Olesen, NE, Jones, DS, Kozyra, A, Löbmann, K, Paluch, K, Brennan, CM, Holm, R, Healy, AM, Andrews, GP & Rades, T 2015, 'Comparative Study of Different Methods for the Prediction of Drug-Polymer Solubility', Molecular Pharmaceutics, bind 12, nr. 9, s. 3408–3419. https://doi.org/10.1021/acs.molpharmaceut.5b00423

    Comparative Study of Different Methods for the Prediction of Drug-Polymer Solubility. / Knopp, Matthias Manne; Tajber, Lidia; Tian, Yiwei; Olesen, Niels Erik; Jones, David S.; Kozyra, Agnieszka; Löbmann, Korbinian; Paluch, Krzysztof; Brennan, Claire Marie; Holm, René; Healy, Anne Marie; Andrews, Gavin P.; Rades, Thomas.

    I: Molecular Pharmaceutics, Bind 12, Nr. 9, 2015, s. 3408–3419.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    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

    Y1 - 2015

    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

    VL - 12

    SP - 3408

    EP - 3419

    JO - Molecular Pharmaceutics

    JF - Molecular Pharmaceutics

    SN - 1543-8384

    IS - 9

    ER -