Influence of Polymer Molecular Weight on Drug-Polymer Solubility: A Comparison between Experimentally Determined Solubility in PVP and Prediction Derived from Solubility in Monomer
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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.
Originalsprog | Engelsk |
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Tidsskrift | Journal of Pharmaceutical Sciences |
Vol/bind | 104 |
Udgave nummer | 9 |
Sider (fra-til) | 2905–2912 |
Antal sider | 8 |
ISSN | 0022-3549 |
DOI | |
Status | Udgivet - 3 mar. 2015 |
ID: 137373672