title: Preparation and optimization of resveratrol nanosuspensions by antisolvent precipitation using Box-Behnken design.
abstract: Resveratrol, a natural polyphenolic component, has inspired considerable interest for its extensive physiological activities. However, the poor solubility of resveratrol circumscribes its therapeutic applications. The purpose of this study was to optimize and prepare resveratrol nanosuspensions using the antisolvent precipitation method. The effects of crucial formulation and process variables (drug concentration, stabilizer, and surfactant contents) on particle size were investigated by utilizing a three-factor three-level Box-Behnken design (BBD) to perform this experiment. Different mathematical polynomial models were used to identify the impact of selected parameters and to evaluate their interrelationship for predictive formulation purposes. The optimal formulation consisted of drug 29.2 (mg/ml), polyvinylpyrrolidone (PVP) K17 0.38%, and F188 3.63%, respectively. The morphology of nanosuspensions was found to be near-spherical shaped by scanning electron microscopy (SEM) observation. The X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) analysis confirmed that the nanoparticles were in the amorphous state. Furthermore, in comparison to raw material, resveratrol nanosuspensions showed significantly enhanced saturation solubility and accelerated dissolution rate resulting from the decrease in particle size and the amorphous status of nanoparticles. Meanwhile, resveratrol nanosuspensions exhibited the similar antioxidant potency to that of raw resveratrol. The in vivo pharmacokinetic study revealed that the C max and AUC0→∞ values of nanosuspension were approximately 3.35- and 1.27-fold greater than those of reference preparation, respectively. Taken together, these results suggest that this study provides a beneficial approach to address the poor solubility issue of the resveratrol and affords a rational strategy to widen the application range of this interesting substance.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, 44 Wenhua Xilu, Jinan, 250012, People's Republic of China.
authors.forename: Jifu
authors.initials: J
authors.lastname: Hao
authors.forename: Yun
authors.initials: Y
authors.lastname: Gao
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Jimei
authors.initials: J
authors.lastname: Zhang
authors.forename: Qiankui
authors.initials: Q
authors.lastname: Li
authors.forename: Zhongxi
authors.initials: Z
authors.lastname: Zhao
authors.forename: Jiyong
authors.initials: J
authors.lastname: Liu
mesh_terms: D003102:Colloids / Q000737:chemistry*; D003198:Computer Simulation; D004058:Diffusion; D004339:Drug Compounding / Q000379:methods; D015195:Drug Design; D004355:Drug Stability; D005590:Fractional Precipitation / Q000379:methods*; D008956:Models, Chemical; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure*; D010316:Particle Size; D000077185:Resveratrol; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013267:Stilbenes; D013501:Surface-Active Agents / Q000737:chemistry*
chemical_list: D003102:Colloids; D053769:Nanocapsules; D012997:Solvents; D013267:Stilbenes; D013501:Surface-Active Agents; D000077185:Resveratrol