Crystallization inhibition in solid dispersions of MK-0591 and poly(vinylpyrrolidone) polymers

The effects of poly(vinylpyrrolidone) (PVP) molecular weight, composition, and content on the crystallization of a model drug, MK-0591 (Form I), were investigated. Solid dispersions of crystalline MK-0591 with PVP homopolymers of different molecular weights (2500-1 x 10(6) g/mol) and with a copolymer containing poly(vinyl acetate) (PVA), (PVP/VA, 60:40, 5.8 x 10(4) g/mol) were prepared by the solvent method. MK-0591 in the solid dispersions was found to be X-ray amorphous. One glass transition temperature (T-g) was observed suggesting drug-polymer miscibility. The T-g values were higher than predicted by the Gordon-Taylor equation, indicating drug-polymer interactions. The extent of crystallization inhibition increased with PVP molecular weight and, for a comparable PVP molecular weight, the homopolymer was more effective in the crystallization inhibition of the drug than the copolymer. The first onset temperature of crystallization (T-c(obs)) increased with polymer content. The T-c(obs) values (normalized to polymer content) were a function of the difference between the T-g of the polymer and drug. For PVP K-90, K-30, and K-17 dispersions, the T-c(obs) values increased proportionally to the T-g of the dispersions; However, for PVP K-12 and PVP/VA, the increase in T-c(obs) values corresponded to a small decrease in the T-g values of the dispersions. This result suggests that additional factors other than the reduction in mobility affect the crystallization behavior of MK-0591 in the solid dispersions, such as specific interactions. By Fourier transform-infrared spectroscopy, changes in the carbonyl-stretching band of PVP in the solid dispersions were observed. The existence of an ion-dipole interaction between COO-Na+ of the drug and the cyclic amide group of PVP was postulated. (C) 2000 Wiley-Liss, Inc. and the American Pharmaceutical Association.