Box-Behnken效应面法优化盐酸达克罗宁温敏凝胶的处方工艺  

Formula optimization of dyclonine hydrochloride thermosensitive gel by Box-Behnken response surface methodology

作　　者：李娇 潘娇娇 徐丽芝 陈卫东 王淑君[4] 杨瑞 LI Jiao;PAN Jiao-jiao;XU Li-zhi;CHEN Wei-dong;WANG Shu-jun;YANG Rui(College of Pharmacy,Anhui University of Chinese Medicine,Hefei 230012;Yangtze Delta Drug Advanced Research Institute,Nantong Jiangsu 226133;Jiangsu Aidi Nano-Biomedical Co.,Ltd.,Nantong Jiangsu 226100;Shenyang Pharmaceutical University,Shenyang 110016;The Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110034)

机构地区：[1]安徽中医药大学药学院,合肥230012 [2]长三角药物高等研究院,江苏南通226133 [3]江苏艾迪纳米生物医药有限公司,江苏南通226100 [4]沈阳药科大学,沈阳110016 [5]辽宁中医药大学附属第二医院,沈阳110034

出　　处：《中南药学》2024年第4期936-942,共7页Central South Pharmacy

摘　　要：目的制备盐酸达克罗宁温敏凝胶(DH-Gel),并对其进行稳定性、体外释放和刺激性考察。方法以胶凝温度为评价指标,采用单因素试验和Box-Behnken效应面法优化DH-Gel处方;以性状、pH、胶凝温度、药物含量变化为评价指标,考察DH-Gel在不同条件下的稳定性;以扩散池法考察凝胶体外释药行为;采用家兔眼刺激性试验考察DH-Gel的刺激性。结果最佳处方是盐酸达克罗宁用量为1%,泊洛沙姆407用量为19.39%,泊洛沙姆188用量为1.96%,羟丙基甲基纤维素用量为0.30%,苯甲酸钠用量为0.01%;在高温和低温条件下稳定性良好;凝胶的体外释药遵从Ritger-Peppas动力学方程,为Fick扩散;DH-Gel组刺激性程度小于盐酸达克罗宁溶液组。结论制备的DH-Gel具有理想的胶凝温度,能使药物更持久有效地黏附在给药部位,具有给药方便等优点。Objective To prepare dyclonine hydrochloride thermosensitive gel(DH-Gel),and to determine its stability,in vitro release and irritation.Methods The gelation temperature was taken as the evaluation index.The formula of DH-Gel was optimized by single factor test and Box-Behnken response surface methodology.The changes in character,pH,gelation temperature and drug content were used as evaluation indexes,and the stability of DH-Gel under different conditions was measured.The drug release behavior of the gel was determined by diffusion pool method.The irritation of DH-Gel was investigated by rabbit eye irritation test.Results The best formula of DH-Gel was dyclonine hydrochloride 1%,poloxamer 40719.39%,poloxamer 1881.96%,hydroxypropyl methyl cellulose 0.30%,and sodium benzoate 0.01%.The preparation was stable under both high and low temperature.The drug release was in compliance with Ritger-Peppas equation.Dyclonine hydrochloride release from the thermosensitive gel displayed the Fick’s diffusion.The irritation degree of the DH-Gel group was lower than that of dyclonine hydrochloride solution group.Conclusion DH-Gel prepared in this experiment has an ideal gelation temperature,which can make the drug adhere to the drug site more persistently and effectively,facilitating the administration.

关 键 词：盐酸达克罗宁 温敏凝胶 BOX-BEHNKEN效应面法 体外释放 

分 类 号：R945[医药卫生—微生物与生化药学]