用Box-Behnken效应面法优化穿心莲内酯纳米乳原位凝胶处方工艺研究

Optimization of In-situ Gel Formulation of Andrographolide Nanoemulsion by Box-Behnken

目的:采用Box-Behnken效应面法优化穿心莲内酯纳米乳原位凝胶的处方,为中药经皮给药制剂的研究与开发提供参考。方法:以泊洛沙姆188(P188)和泊洛沙姆407(P407)为凝胶基质,采用凝胶基质的质量分数为考察因素,凝胶温度为考察指标,通过二项式拟合分析得到方程,并建立胶凝温度与2个考察因素之间的数学关系,采用星点设计-效应面法优化穿心莲内酯纳米乳原位凝胶的处方,并对优化处方进行验证。结果:凝胶温度与考察因素存在可信定量关系,且二项式拟合方程置信度高。穿心莲内酯纳米乳原位凝胶的最佳处方为20.00%泊洛沙姆407和5.00%泊洛沙姆188;凝胶温度为(33.8±0.2)℃,处方制备重复性高。结论:该方法适用于穿心莲内酯纳米乳原位凝胶的处方优化,建立的模型预测性良好,优化的制备方法稳定,胶凝温度适宜,可为穿心莲内酯经皮给药制剂的开发提供参考。

Objective:To optimize the in-situ gel formulation of andrographolide nanoemulsion using the Box-Behnken response surface methodology to provide references for the research and development of transdermal drug delivery systems of Chinese medicine.Methods:A quadratic regression equation was obtained through polynomial fitting analysis with poloxamer 188(P188)and poloxamer 407(P407)as gel matrices,the mass fractions of gel matrices as the investigation factors,and gel temperature as the investigation index,and the mathematical relationship between gel temperature and the two factors were established.The Box-Behnken design-response surface methodology was used to optimize the in-situ gel formulation of andrographolide nanoemulsion,and the optimized formulation was validated.Results:There was a reliable quantitative relationship between gel temperature and the investigation factors,and the quadratic regression equation had a high degree of confidence.The optimal formulation for andrographolide nanoemulsion in-situ gel was determined as 20.00%P407 and 5.00%P188,with a gel temperature of(33.8±0.2)℃.The formulation preparation showed high reproducibility.Conclusion:This method is suitable for optimizing the formulation of andrographolide nanoemulsion in-situ gel.The established model has good predictive performance,and the optimized preparation method is stable with an appropriate gel temperature.This research provides references for the development of andrographolide transdermal drug delivery systems.