Effect of polyvinylpyrrolidone on the crystallinity and dissolution rate of solid dispersions of the antiinflammatory CI-987

Abstract

Solid dispersions of CI-987 (5-{[3,5-bis(l,l-dimethylethyI)-4-hydroxyphcnyl]-methylene}-2,4-thiazolidinedione) having varying concentrations of polyvinylpyrrolidone (PVP K 28–32), were prepared in an attempt to improve the dissolution rate of CI-987. The physical characteristics of these solid dispersions were investigated by X-ray diffraction and dissolution rate studies. The dissolution rate of CI-987 can be significantly increased by increasing the weight fraction of PVP in the solid dispersions. The maximum dissolution rate occurred with the solid dispersion having a PVP weight fraction of 0.81 where the CI-987 dissolution rate is 15-times greater than that for CI-987 in the absence of PVP and where X-ray diffraction suggests that CI-987 exists in a totally amorphous state. As the PVP weight fractions decreased from 0.81, the dispersions displayed increasing degrees of crystallinity. The dissolution rate vs PVP weight fraction plot displayed three distinct regions: at low PVP (high drug) weight fractions, a drug-controlled region; at intermediate PVP weight fractions, a region where changes in the degree of crystallinity of CI-987 play a major role; and at high PVP (low drug) weight fractions, a PVP-controlled region.