基于Box-Behnken Design设计优化白藜芦醇纳米混悬剂的制备工艺

Optimization of preparation process of resveratrol nanosuspension based on Box-Behnken Design

目的优化白藜芦醇纳米混悬剂的最佳制备工艺。方法采用反溶剂沉淀法制备白藜芦醇纳米混悬剂,以聚乙烯吡咯烷酮PVPK 17 PF为助悬剂,泊洛沙姆F188为表面活性剂,以粒径及多分散指数为响应值,应用Box-Behnken Design响应面实验设计优化白藜芦醇纳米混悬剂的最佳处方,并采用桨法进行体外释放实验评价其药物释放特征。结果优化后的纳米混悬剂处方为:白藜芦醇的质量浓度为29.2 mg/mL,助悬剂PVP K17PF的质量分数为0.38%,表面活性剂Poloxmer 188质量浓度为3.63 mg/mL。所制备纳米混悬剂的粒径大小为145 nm左右,在1 h的累积释放接近80%,释放机制为扩散作用为主。结论将白藜芦醇制备成纳米混悬剂可以提高白藜芦醇的溶出度,为难溶性药物白藜芦醇的进一步开发奠定了基础。

Objective To optimize the best preparation process of resveratrol nanosuspension.Methods Resveratrol nanosuspension was prepared by antisolvent precipitation method with polyvinyl pyrrolidone PVP17PF as suspension agent and poloxamer F188 as surfactant.The optimized formulation of resveratrol nanosuspension was screeed by Box-Behnken Design(BBD)response surface experiment with particle size and polydispersity index as response values.The drug release characteristics of resveratrol nanosuspension was evaluated by paddle method in vitro.Results The optimized formulation of resveratrol nanosuspension was as follows:the content of resveratrol was 29.2 mg/mL,the ratio of PVP K17PF was 0.38%and the concentration of Poloxmer 188 was 3.63 mg/mL.The particle size of prepared resveratrol nanosuspension was about 145 nm.The cumulative release of resveratrol nanosuspension in 1 h was close to 80%.The release mechanism was dominated by diffusion.Conclusion The preparation of resveratrol nanosuspension may improve the dissolution of resveratrol,which can lay a foundation for the further development of insoluble drug resveratrol.