Box-Behnken响应面法优化“三六九”复方膏剂的制备工艺

Formulation Optimization of “Three-Six-Nine” Ointment by Box-Behnken Response Surface Method

关键词:  “三六九”凝胶膏剂  乳化超声-旋转蒸发法  纳米脂质载药系统  Box-Behnken响应面法  质量控制

Key words:  “Three-Six-Nine” gel paste  emulsification ultrasound-rotary evaporation method  nano-lipid drug delivery system  Box-Behnken response surface method  quality control

摘要:

目的 优化“三六九”方剂中挥发油组分的提取工艺，制备“三六九”缓释凝胶膏剂。方法 采用Box-Behnken效应面法，以“三六九”组方挥发油得率为响应指标，原料粒度、萃取温度、萃取时间为考察因素，结合二项式方程拟合试验结果以确定组方挥发油提取的最优提取条件，并采用乳化超声-旋转蒸发法制备基于 β-环糊精纳米脂质载药的凝胶膏剂，以感官评价、赋型性测定、皮肤追随性、耐寒性评价、耐热性评价作为其质量评价标准。结果 “三六九”方剂挥发油的最佳处方工艺为原料粒度过40目筛，萃取时间3 h，萃取温度50 ℃。提取得到挥发油量(0.469±0.021)mL，即挥发油得(1.78±0.08)mL·g^-1。评价结果显示，“三六九”凝胶膏剂具有稳定的赋型性、耐热性与耐寒性，同时具有较好的黏性与皮肤适贴性。结论 Box-Behnken响应面优化法应用简便、预测性好，制备得到的“三六九”凝胶膏剂质量较好。

Abstract:

OBJECTIVE To optimize the extraction process of volatile oil components in “Three-Six-Nine” ointment to prepare the “Three-Six-Nine” sustained-release gel paste. METHODS The Box-Behnken response surface method was used to optimize the extraction process of the volatile oil of the “Three-Six-Nine” ointment. The receiving rate of the volatile oil was taken as the evaluation indicator, and the particle size of raw material, extraction temperature and extraction time were taken as the investigation factors. The binomial equation was used to fit the experimental results to verify the optimal extraction conditions. The nano-lipid drug delivery system based on β-cyclodextrin was prepared by emulsification ultrasound-rotary evaporation method. The quality evaluation criteria were sensory evaluation, formativity measurement, skin followability, cold resistance evaluation and heat resistance evaluation. RESULTS The best extraction process of the volatile oil of “Three-Six-Nine” ointment was as follows: raw material particle size over 40 mesh screen, with extraction time of 3 h and extraction temperature of 50 ℃. The amount of volatile oil extracted was (0.469±0.021)mL, the yield of volatile oil was (1.78±0.08)mL·g^-1. The results implied “Three-Six-Nine” ointment shown stable formability, heat and cold resistance, and had good adhesion and skin adhesion. CONCLUSION Box-Behnken response surface optimization method is simple and predictable, the prepared “Three-Six-Nine” gel paste has good quality.