Investigation of Drug–Polymer Miscibility and Solubilization on Meloxicam Binary Solid Dispersion
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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.
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.
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 Cmax (3.25 times) and AUC (2.88 times) than pure MLX.
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.
KeywordsMeloxicam Amorphous solid dispersion Dissolution Miscibility Precipitation inhibition Stability
High acknowledgments are given to Lin Yang, Fuqi Fei, and Yuzhi Wang (Zhejiang University of Technology) for assisting pharmacokinetic study.
This work was funded by Project 21606203 of the Natural Science Foundation of China.
Compliance with Ethical Standards
The experimental protocols of the animal studies followed the Animal Ethics Committee of Zhejiang University of Technology. And all operations involving animals were conducted with the guidelines of the National Institutes of Health Guide for Care and Use of Laboratory Animals.
Conflict of Interest
The authors declare that they have no conflict of interest.
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