甘草黄酮纳米结晶的制备与评价

Preparation and characterization of licorice flavonoids nanocrystals

目的:优选甘草黄酮纳米结晶的制备工艺并对所得纳晶进行初步评价。方法:以超声辅助-反溶剂沉淀法制备纳米混悬液,采用正交试验L9(34),考察药物浓度、药物与表面活性剂的质量比、注入速度、超声时间对纳晶粒径及其分布的影响,并进一步优选稳定剂及冻干保护剂;比较所得纳晶与原药的平衡溶解度和体外溶出度。结果:最优处方工艺为:药物浓度20 mg·mL^(-1),稳定剂为10 mg·mL^(-1) SDS、5 mg·mL^(-1)PEG-400、0.2%PVA,注入速度0.5 mL·min-1,超声7 min,加入5%乳糖作为冻干保护剂;此条件下制得纳晶冻干前后粒径分别为(61.70±1.40)nm和(108.9±1.67)nm,呈电中性、粒径较均匀;冻干粉载药量31.04%,原料药和纳晶在pH6.8 PBS中的溶解度分别为3.41 mg·mL^(-1)和7.37 mg·mL^(-1),2 min时溶出率为8.33%和55.91%。结论:该纳米结晶制备工艺简便易行,可显著改善甘草黄酮的溶解度和溶出度。

OBJECTIVE To fabricate and characterize nanocrystals of licorice flavonoids.METHODS Nanosuspension was prepared by ultrasonic assisted anti-solvent precipitation method.Several key factors were optimized by orthogonal L9（34）design using particle size as indicator,including drug concentration,weight ratio of drug and surfactant,injection speed and ultrasonication time.Other co-stabilizers and lyoprotectants were further selected.Obtained nanocrystals were compared with raw materials on their equilibrium solubility and in vitro dissolution.RESULTS Optimal process was as follows：20 mg·mL^-1of licorice flavonoid,10 mg·mL^-1SDS,5 mg·mL^-1PEG-400,0.2% PVA as stabilizers,5%lactose as lyoprotectant,treated by ultrasonic for 7 min,and injected at rate of 0.5 mL·min-1.Obtained nanocrystals possessed a mean particle size of 61.70 and108.9 nm before and after lyophilization,respectively.Powder was electrically neutral with a relatively uniform size and a drug load of 31.04%.Nanocrystals and raw materials showed equilibrium solubility values of 3.41 and 7.37 mg·mL^-1in PBS（pH=6.8）,and released8.33%and55.91% of total drug load after 2 min in the same medium,respectively.CONCLUSION The preparation process for nanocrystals of licorice flavonoids is simple and feasible,can significantly improve solubility and dissolution performance.