Influence of Polymer Molecular Weight on Drug–Polymer Solubility

A Comparison between Experimentally Determined Solubility in PVP and Prediction Derived from Solubility in Monomer

Matthias Manne Knopp, Niels Erik Olesen, Per Holm, Peter Langguth, René Holm, Thomas Rades

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    In this study, the influence of polymer molecular weight on drug–polymer solubility was investigated using binary systems containing indomethacin (IMC) and polyvinylpyrrolidone (PVP) of different molecular weights. The experimental solubility in PVP, measured using a differential scanning calorimetry annealing method, was compared with the solubility calculated from the solubility of the drug in the liquid analogue N-vinylpyrrolidone (NVP). The experimental solubility of IMC in the low-molecular-weight PVP K12 was not significantly different from that in the higher molecular weight PVPs (K25, K30, and K90). The calculated solubilities derived from the solubility in NVP (0.31–0.32 g/g) were found to be lower than those experimentally determined in PVP (0.38–0.40 g/g). Nevertheless, the similarity between the values indicates that the analogue solubility can provide valuable indications on the solubility in the polymer. Hence, if a drug is soluble in an analogue of the polymer, it is most likely also soluble in the polymer. In conclusion, the solubility of a given drug–polymer system is determined by the strength of the drug–polymer interactions rather than the molecular weight of the polymer. Therefore, during the first screenings for drug solubility in polymers, only one representative molecular weight per polymer is needed
    OriginalsprogEngelsk
    TidsskriftJournal of Pharmaceutical Sciences
    Vol/bind104
    Udgave nummer9
    Sider (fra-til)2905-2912
    ISSN0022-3549
    DOI
    StatusUdgivet - 2015

    Citer dette

    Knopp, Matthias Manne ; Olesen, Niels Erik ; Holm, Per ; Langguth, Peter ; Holm, René ; Rades, Thomas. / Influence of Polymer Molecular Weight on Drug–Polymer Solubility : A Comparison between Experimentally Determined Solubility in PVP and Prediction Derived from Solubility in Monomer. I: Journal of Pharmaceutical Sciences. 2015 ; Bind 104, Nr. 9. s. 2905-2912.
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    title = "Influence of Polymer Molecular Weight on Drug–Polymer Solubility: A Comparison between Experimentally Determined Solubility in PVP and Prediction Derived from Solubility in Monomer",
    abstract = "In this study, the influence of polymer molecular weight on drug–polymer solubility was investigated using binary systems containing indomethacin (IMC) and polyvinylpyrrolidone (PVP) of different molecular weights. The experimental solubility in PVP, measured using a differential scanning calorimetry annealing method, was compared with the solubility calculated from the solubility of the drug in the liquid analogue N-vinylpyrrolidone (NVP). The experimental solubility of IMC in the low-molecular-weight PVP K12 was not significantly different from that in the higher molecular weight PVPs (K25, K30, and K90). The calculated solubilities derived from the solubility in NVP (0.31–0.32 g/g) were found to be lower than those experimentally determined in PVP (0.38–0.40 g/g). Nevertheless, the similarity between the values indicates that the analogue solubility can provide valuable indications on the solubility in the polymer. Hence, if a drug is soluble in an analogue of the polymer, it is most likely also soluble in the polymer. In conclusion, the solubility of a given drug–polymer system is determined by the strength of the drug–polymer interactions rather than the molecular weight of the polymer. Therefore, during the first screenings for drug solubility in polymers, only one representative molecular weight per polymer is needed",
    author = "Knopp, {Matthias Manne} and Olesen, {Niels Erik} and Per Holm and Peter Langguth and Ren{\'e} Holm and Thomas Rades",
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    Influence of Polymer Molecular Weight on Drug–Polymer Solubility : A Comparison between Experimentally Determined Solubility in PVP and Prediction Derived from Solubility in Monomer. / Knopp, Matthias Manne; Olesen, Niels Erik; Holm, Per; Langguth, Peter; Holm, René; Rades, Thomas.

    I: Journal of Pharmaceutical Sciences, Bind 104, Nr. 9, 2015, s. 2905-2912.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - Influence of Polymer Molecular Weight on Drug–Polymer Solubility

    T2 - A Comparison between Experimentally Determined Solubility in PVP and Prediction Derived from Solubility in Monomer

    AU - Knopp, Matthias Manne

    AU - Olesen, Niels Erik

    AU - Holm, Per

    AU - Langguth, Peter

    AU - Holm, René

    AU - Rades, Thomas

    PY - 2015

    Y1 - 2015

    N2 - In this study, the influence of polymer molecular weight on drug–polymer solubility was investigated using binary systems containing indomethacin (IMC) and polyvinylpyrrolidone (PVP) of different molecular weights. The experimental solubility in PVP, measured using a differential scanning calorimetry annealing method, was compared with the solubility calculated from the solubility of the drug in the liquid analogue N-vinylpyrrolidone (NVP). The experimental solubility of IMC in the low-molecular-weight PVP K12 was not significantly different from that in the higher molecular weight PVPs (K25, K30, and K90). The calculated solubilities derived from the solubility in NVP (0.31–0.32 g/g) were found to be lower than those experimentally determined in PVP (0.38–0.40 g/g). Nevertheless, the similarity between the values indicates that the analogue solubility can provide valuable indications on the solubility in the polymer. Hence, if a drug is soluble in an analogue of the polymer, it is most likely also soluble in the polymer. In conclusion, the solubility of a given drug–polymer system is determined by the strength of the drug–polymer interactions rather than the molecular weight of the polymer. Therefore, during the first screenings for drug solubility in polymers, only one representative molecular weight per polymer is needed

    AB - In this study, the influence of polymer molecular weight on drug–polymer solubility was investigated using binary systems containing indomethacin (IMC) and polyvinylpyrrolidone (PVP) of different molecular weights. The experimental solubility in PVP, measured using a differential scanning calorimetry annealing method, was compared with the solubility calculated from the solubility of the drug in the liquid analogue N-vinylpyrrolidone (NVP). The experimental solubility of IMC in the low-molecular-weight PVP K12 was not significantly different from that in the higher molecular weight PVPs (K25, K30, and K90). The calculated solubilities derived from the solubility in NVP (0.31–0.32 g/g) were found to be lower than those experimentally determined in PVP (0.38–0.40 g/g). Nevertheless, the similarity between the values indicates that the analogue solubility can provide valuable indications on the solubility in the polymer. Hence, if a drug is soluble in an analogue of the polymer, it is most likely also soluble in the polymer. In conclusion, the solubility of a given drug–polymer system is determined by the strength of the drug–polymer interactions rather than the molecular weight of the polymer. Therefore, during the first screenings for drug solubility in polymers, only one representative molecular weight per polymer is needed

    U2 - 10.1002/jps.24410

    DO - 10.1002/jps.24410

    M3 - Journal article

    VL - 104

    SP - 2905

    EP - 2912

    JO - Journal of Pharmaceutical Sciences

    JF - Journal of Pharmaceutical Sciences

    SN - 0022-3549

    IS - 9

    ER -