龙凯花　黄昕玥　王春柳

摘要：目的 采用Box-Behnken效應面法优化丹皮酚纳米结构脂质载体（NLC）温度敏感型原位凝胶的处方，并对其体外释放性能进行考察，为经皮给药制剂的研究提供参考。方法 以泊洛沙姆407和泊洛沙姆188质量分数为考察因素，胶凝温度为考察指标，通过二项式模型及多元线性回归模型拟合并建立胶凝温度与2个考察因素之间的数学关系，采用Box-Behnken效应面法，对丹皮酚NLC温敏型原位凝胶的处方进行优化，并考察该制剂的体外释药特性。结果 胶凝温度与2个考察因素之间存在可信定量关系，且二项式模型较多元线性模型置信度高。丹皮酚NLC温敏型原位凝胶的最佳处方为22.90%泊洛沙姆407和3.34%泊洛沙姆188，胶凝温度为（33.4±0.1）℃，24 h内丹皮酚NLC原位凝胶的累积释放量为51.19%。结论 该方法适用于丹皮酚NLC温敏型原位凝胶的处方优化，建立的数学模型预测性良好，优选的处方可为丹皮酚经皮给药制剂的开发提供参考。

关键词：温敏型原位凝胶；丹皮酚；纳米结构脂质载体；星点设计-效应面法；经皮给药

DOI：10.3969/j.issn.1005-5304.2018.06.018

中图分类号：R283.5 文献标识码：A 文章编号：1005-5304（2018）06-0073-04

Optimization of Paeonol NLC Thermosensitive Gel Formulation by

Box-Behnken Response Surface Methodology

LONG Kai-hua1， HUANG Xin-yue1， WANG Chun-liu2， MU Jun3， LI Ye2

1. Xi'an Peihua University， Xi'an 710125， China； 2. Shaanxi Academy of Traditional Chinese Medicine， Xi'an 710003， China； 3. Shaanxi University of Chinese Medicine， Xianyang 712046， China

Abstrsct： Objective To optimize the formulation of paeonol nanostructured lipid carrier （NLC） thermosensitive in situ gel through Box-Behnken response surface method； To investigate its release properties in vitro to provide references for the study of transdermal drug delivery system. Methods Taking mass fraction of poloxamer 407 and poloxamer 188 as the factors， the gelling temperature as the index， the mathematical relationship between the gelling temperature and two factors was established by binomial model and multivariate linear regression model. The Box-Behnken response surface method was used to optimize the formulation of paeonol NLC thermosensitive in situ gel， and the in vitro release characteristics of the preparation was investigated. Results There was a credible quantitative relationship between the gelling temperature and the 2 factors， and the binomial model was more reliable than the multivariate linear model. The best prescriptions of paeonol NLC thermosensitive in situ gel were 22.90% poloxamer 407 and 3.34% poloxamer 188； gelling temperature was （33.4±0.1）℃， and the cumulative release amount of paeonol in situ gel in 24 h was 51.19%. Conclusion This method is suitable for the formulation optimization of paeonol NLC thermosensitive in-situ gel， and the established mathematical model has good predictability. The optimized formulation can provide references for the development of paeonol transdermal preparation.

Keywords： in situ thermosensitive gel； paeonol； nanostructured lipid carrier； central composite design - response surface method； transdermal drug delivery

丹皮酚又称牡丹酚，主要是从萝摩科植物徐长卿Cynanchum paniculatum（Bunge）Kitagawa的干燥根或全草和毛茛科芍药属植物牡丹Paeonia fruticosa Andr、芍药P.lacti flora Pall.的根皮中提取分离出来的活性成分。大量研究表明，丹皮酚具有良好的抗炎、抗过敏及抗感染作用[1-3]，但由于丹皮酚的脂溶性极强，生物利用度极低，具有易挥发、易氧化、生物半衰期短等缺点，影响其制剂的稳定性和生物利用度[4-6]。纳米给药系统具有增溶难溶性药物、提高药物生物利用度的特点，能够明显改善药物及制剂的突释效应，延长药物作用时间，减少用药次数，提高患者依从性。……