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
李娇 1潘娇娇 1徐丽芝 1陈卫东 2王淑君 3杨瑞4
作者信息
- 1. 安徽中医药大学药学院,合肥 230012;长三角药物高等研究院,江苏 南通 226133;江苏艾迪纳米生物医药有限公司,江苏 南通 226100
- 2. 安徽中医药大学药学院,合肥 230012
- 3. 沈阳药科大学,沈阳 110016
- 4. 辽宁中医药大学附属第二医院,沈阳 110034
- 折叠
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.
Abstract
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 407 19.39％,poloxamer 188 1.96％,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Key words
dyclonine hydrochloride/thermosensitive gel/Box-Behnken response surface methodology/in vitro release引用本文复制引用
出版年
2024
NETL
NSTL
万方数据