Influence of Polymer Molecular Weight on Drug-Polymer Solubility: A Comparison between Experimentally Determined Solubility in PVP and Prediction Derived from Solubility in Monomer.
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.
Department of Biologics and Pharmaceutical Science, H. Lundbeck A/S, Valby, DK-2500, Denmark.|School of Pharmacy, Johannes Gutenberg University Mainz, Mainz, D-55099, Germany.
Matthias Manne
MM
Knopp
Department of Biologics and Pharmaceutical Science, H. Lundbeck A/S, Valby, DK-2500, Denmark.|NSM, Research Unit for functional Biomaterials, Roskilde University, Roskilde, DK-4000, Denmark.
Niels Erik
NE
Olesen
Department of Biologics and Pharmaceutical Science, H. Lundbeck A/S, Valby, DK-2500, Denmark.
Per
P
Holm
School of Pharmacy, Johannes Gutenberg University Mainz, Mainz, D-55099, Germany.
Peter
P
Langguth
Department of Biologics and Pharmaceutical Science, H. Lundbeck A/S, Valby, DK-2500, Denmark.
René
R
Holm
Department of Pharmacy, University of Copenhagen, Copenhagen, DK-2100, Denmark.
Thomas
T
Rades
D002152:Calorimetry, Differential Scanning / Q000379:methods; D007213:Indomethacin / Q000737:chemistry; D008970:Molecular Weight; D011108:Polymers / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry*; D011760:Pyrrolidinones / Q000737:chemistry; D012995:Solubility
D011108:Polymers; D011760:Pyrrolidinones; C042670:N-vinyl-2-pyrrolidinone; D011205:Povidone; D007213:Indomethacin
DSC; Flory-Huggins; Gordon-Taylor; PVP; amorphous; indomethacin; molecular weight; polymer; solid dispersion; spray drying