Study on Preparation of Triptolide-glycyrrhetic Acid Compound Microemulsion and Its Physicochemical Properties and in vitro Release Characteristics
- VernacularTitle:雷公藤甲素-甘草次酸复方微乳的制备及其理化性质和体外释药特性研究
- Author:
Heng ZHENG
1
;
Xiaodong LI
1
;
Xiaoying ZHAI
1
;
Shuying DONG
1
;
Duo ZHANG
1
;
Rui YANG
2
Author Information
1. Dept. of Dermatology，Central Hospital Affiliated to Shenyang Medical College，Shenyang 110024，China
2. Academy of Traditional Chinese Medi cine of Liaoning Province，Shenyang 110034，China
- Publication Type:Journal Article
- Keywords:
Triptolide;
Glycyrrhetic acid;
Compound microemulsion;
UPLC;
Pseudo-ternary phase diagrams;
Formula optimization;
in vitro release rate
- From:
China Pharmacy
2019;30(12):1655-1660
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE： To establish content determination method of Triptolide-glycyrrhetic acid compound microemulsion， optimize the formula and investigate its physicochemical properties and release rate in vitro. METHODS： The content of Triptolide- glycyrrhetic acid compound microemulsion was determined by UPLC. The determination was performed on ACQUITY UPLC BEH C18 column with mobile phase consisted of 0.1％ formic acid aqueous solution-acetonitrile （gradient elution） at the flow rate of 0.4 mL/min. The column temperature was 40 ℃. The detection wavelength was set at 218 nm， and sample size was 5 μL. Pseudo-ternary phase diagrams were drawn by water titration method. Using oil phase， surfactants and co-surfactants as index， the formula was optimized， and in intro release characteristics was investigated by in vitro release test. RESULTS： The linear range of triptolide and glycyrrhetinic acid were 1-40 μg/mL（r＝0.999 7） and 10-400 μg/mL（r＝0.999 8）， respectively. The limits of quantitation were 0.5 and 0.8 μg/mL； the limits of detection were 0.1 and 0.2 μg/mL. RSDs of precision， stability and reproducibility tests were all less than 2％. Average recoveries were 100.32％-101.15％ （RSD＝0.36％， n＝6）， 99.78％-101.42％ （RSD＝0.59％，n＝6）. The optimal formula included that medium chain triglyceride as oil phase， polyethylene glycol hydroxy stearate as surfactants， ethanol as co-surfactants， water as water phase， the proportion of them was 8 ∶ 28 ∶ 14 ∶ 50. The obtained microemulsion was O/W type， being transparent and clear， with average diameter， average polydispersity index and average viscosity of （62.38±3.44） nm， 0.096±0.001 and （26.84±1.10） mPa·S. Within 24 h， cumulative release rates of triptolide and glycyrrhetinic acid in obtained microemulsion were 99.8％ and 99.7％ （in PBS pH 2.0）， 99.3％ and 99.4％ （in PBS pH 7.4）， 98.9％ and 98.4％ （in PBS pH 9.0）， respectively. Triptolide and glycyrrhetinic acid released faster in the single microemulsion than in the compound microemulsion. CONCLUSIONS： Established content determination method is simple and stable. The optimized formula is stable and feasible. Obtained iriptolide-glycyrrhetinic acid compound microemulsion show better sustained-release effect than sigle microemulsion.
