负载甘草次酸微乳的制备及表征Preparation and characterization of microemulsions loaded with glycyrrhetinic acid

为了提高甘草次酸(Glycyrrhetinic acid, GA)在水中的溶解度，促进其经皮吸收，使用加水法制备了甘草次酸微乳(GA microemulsion, GA-ME)。通过测定GA在各辅料中的溶解度，确定了助表面活性剂，采用单因素实验对微乳的主要成分及制备条件进行初步筛选，再利用Box-Behnken响应面法优化配方，并对GA-ME的储藏稳定性、透皮性能、抗氧化性能进行了表征。结果表明：确定二乙二醇单乙醚为助表面活性剂，最优的配方为辛酸/癸酸甘油三酯(Caprylic/capric triglyceride, GTCC)4%、香芹酚2%、Cremophor RH40 14.4%、二乙二醇单乙醚9.6%、水70%，在此配方下制备的微乳GA载量为（2.60±0.05） mg/mL，粒径为（23.21±0.18） nm；GA-ME于4、25、45 ℃下储藏60 d后仍保持澄清透明，粒径稳定在23 nm左右，PDI保持在0.2以下，GA保留率在94%左右，说明该微乳具有良好的储藏稳定性；体外透皮性能实验结果显示，GA-ME中的香芹酚可显著促渗GA，GA在猪皮上的透皮量为28.45 μg/cm2；抗氧化性能实验结果表明，GA-ME的抗氧化效果明显优于将香芹酚或GA单独包载时的。综上，GA-ME可提高GA的溶解度和透皮性能，具有在医药和化妆品领域的应用价值。 In order to improve the solubility of glycyrrhetinic acid (GA) in water and promote its transdermal absorption, water adding method was employed to prepare GA microemulsion(GA-ME). By determining the solubility of GA in excipients, the surfactant aid was determined, the main components and preparation conditions of the microemulsion were preliminarily screened by single-factor experiment, and the formula was optimized by Box-Behnken response surface methodology. The storage stability, transdermal permeation and antioxidant performance of GA-ME were characterized. The results showed that transcutol P was selected as a surfactant aid, and the optimal formula was 4% caprylic/capric triglyceride (GTCC), 2% carvacrol, 14.4% Cremophor RH40,9.6% transcutol P, and 70% water. Under this formula, the GA loading of the microemulsion was (2.60±0.05) mg/mL, with particle size (23.21±0.18) nm. After 60 d of storage at 4, 25 ℃ and 45 ℃, GA-ME maintained clarity with stable particle size around 23 nm, PDI below 0.2, and a GA retention rate about 94%, demonstrating excellent storage stability. In vitro transdermal permeation tests revealed that the carvacrol in GA-ME significantly enhanced GA permeability, achieving a transdermal delivery of 28.45 μg/cm2 on porcine skin. Antioxidant efficacy studies showed that the antioxidant effect of GA-ME was significantly higher than that of GA or carvacrol when encapsulated individually in microemulsions. In conclusion, GA-ME effectively improves the solubility and transdermal permeation of GA, providing valuable reference for its applications in the fields of medicine and cosmetics.