Indexed on: 25 Feb '19Published on: 19 Feb '19Published in: Journal of Pharmaceutical Innovation
Purpose This work aims to study the solubilizing capacity of solid dispersion technology with three kinds of polymers and explore the factors affecting the dissolution and stability of solid dispersions from drug–polymer miscibility, phase solubility, and crystallization inhibition. Methods A meloxicam (MLX) solid dispersion was prepared via the solvent evaporation method with polyvinylpyrrolidone (PVP) K30, polyvinylpyrrolidone-co-vinyl acetate (PVP VA) 6:4 and Soluplus® (SLP), respectively. The drug–polymer miscibility, phase solubility, and precipitation study were applied to evaluate the effect of polymers. And the solubility, dissolution behavior, stability, and pharmacokinetic profile of MLX solid dispersion were researched. Results The PVP K30, PVP VA, and SLP were found to be miscible with MLX in an increasing order of SLP < PVP K30 < PVP VA, and the dissolution behavior of MLX was improved significantly. According to the phase solubility and the saturation solubility results, the PVP K30 had inferior solubilization capacity to MLX. Moreover, because of MLX crystal precipitation (after 43 ± 7.06 min) in the PVP K30 solution, the relatively short supersaturation time was demonstrated by precipitation study. In comparison, PVP VA and SLP had better performance to improve solubility and inhibit crystallization. The stability experiment results indicated that MLX-PVP K30 and MLX-SLP appeared evident crystallization and poor dissolution rate, whereas, the MLX-PVP VA was comparatively stable. In addition, the pharmacokinetics study of MLX-PVP VA showed larger C max (3.25 times) and AUC (2.88 times) than pure MLX. Conclusions This study demonstrated enhancement in solubility and dissolution behavior of MLX, via solid dispersion technology. The well solubility and storage stability of MLX-PVP VA (1:5, w/w) were expected to develop a new oral pharmaceutical product. Besides, in the current study, the drug–polymer miscibility, solubilizing capacity, and inhibition ability of the polymer were systematically discussed. The results indicated that above aspects have positive effects on the screening of polymers for amorphous solid dispersion.