均匀设计-效应面法优化萆薢分清直肠凝胶剂处方及其药代动力学考察

目的:采用均匀设计-效应面法优化萆薢分清直肠凝胶剂的处方,对比该复方口服和直肠给药后在家兔体内的药动学过程,为该复方的现代制剂开发提供参考。方法:以外观、均匀度、黏稠度及pH为综合考察指标,以卡波姆940用量、丙三醇与丙二醇的用量比和NaOH用量为考察因素,采用均匀设计-效应面法优化萆薢分清直肠凝胶的处方。采用HPLC检测口服和直肠给药后血浆中甘草次酸的浓度,以3P97软件计算药动学参数,评价口服和直肠给药后的体内药动学过程。结果:最优处方为1.5%卡波姆940,8%丙三醇,2%丙二醇,1%NaOH,0.03%尼泊金乙酯。直肠给药的药动学参数为药峰浓度(C_(max))(35.144 7±5.272 4)mg·L~(-1),达峰时间(T_(max))(27.114 6±13.358 7)min,药时曲线下面积(AUC_(0-6 h))(5 125.468 5±368.745 9)mg·min·L~(-1)。结论:均匀设计-效应面法适用于萆薢分清直肠凝胶剂的处方优化,建立的数学模型具有较好的预测性,所得凝胶外观细腻、黏度适宜。萆薢分清直肠凝胶剂直肠给药后主要成分在体内吸收迅速、生物利用度较高。

Optimization of Formula of Bixie Fenqing Rectal Gel by Uniform Design-response Surface Methodology and Investigation of Its Pharmacokinetics

Objective: To optimize formula of Bixie Fenqing rectal gel and compare its pharmacokinetics after oral and rectal administration in rabbits. Method: Taking appearance,uniformity,viscosity and pH value as indexes,the amount of carbomer 940,dosage ratio of glycerol and propylene glycol,the amount of NaOH were independent variables,uniform design-response surface methodology was adopted to optimize formulation of the rectal gel.Concentration of glycyrrhetic acid in the plasma was detected by HPLC after oral and rectal administration,3P97 software was employed to calculate the pharmacokinetic parameters and evaluate the pharmacokinetic behavior. Result: The best formula was as following: 1.5% of carbomer 940,8% of glycerol and 2% of propylene glycol,1% of NaOH,0.03% of ethyl p-hydroxybenzoate.The main pharmacokinetic parameters after rectal administration were as follows: Cmax of (35.144 7±5.272 4) mg·L^-1,Tmax of (27.114 6±13.358 7) min,AUC_{0-6 h} of (5 125.468 5±368.745 9) mg·min·L^-1. Conclusion: This established mathematical model has good prediction,the appearance of Bixie Fenqing rectal gel is exquisite,its viscosity is suitable,its main components are absorbed rapidly with high bioavailability.