对乙酰氨基酚温敏凝胶的处方筛选与体外释放研究

目的筛选对乙酰氨基酚温度敏感型原位凝胶处方组成,并对其体外释药进行研究。方法以泊洛沙姆407、泊洛沙姆188为考察因素,以胶凝温度为考察指标,分别用多元线性模型、二次多项式模型描述考察指标和因素之间的数学关系,用中心组合设计-效应面法确定最优处方。采用相似因子法对优化处方与传统栓剂进行体外溶出比较。结果对乙酰氨基酚温度敏感型原位凝胶的最优处方为7.5%药物、21%泊洛沙姆407和18%泊洛沙姆188,胶凝温度为36.2℃。对乙酰氨基酚温敏凝胶与传统栓剂均在45 min内释药达80%,2 h内药物基本释放完全,且释药曲线相似（差异因子f1=2.06%,相似因子f2=68.7%）。结论优化的处方具有适宜的胶凝温度且释药符合要求。

Study on Optimized Formulation and Release of Paracetamol Thermosensitive Gel in Vitro

Objective To optimize the formulation of paracetamol thermosensitive in situ gel and study the in vitro release of paraeetamol from the gel. Methods With the amount of Poloxamer 407 （ P407 ）, Poloxamer 188 （P188） as independent variables, and gel temperature as an dependent variable, the formulation was optimized. Multilinear and quadratic models were used to estimate the relationship between the dependent and the independent variables and to select the optimal formulation using the central composite design-response surface methodology （RSM plus CCD）. Paracetamol dissolution profiles obtained from the gel were compared with the traditional solid suppository by the similarity factor. Results The optimized formulation of paraeetamol thermosensitive gel was 7.5 % drug ,21% P407 and 18% P188. Its gelling temperature was at 36.2℃. The accumulative drug release of the thermosensitive gel and the traditional solid suppository was more than 80% in 45 min, and the drug was completely released in 2 h. The dissolution profiles were similar. Conclusion The optimized formulation of paracetamol thermosensitive gel has an appropriate gelatinization temperature and in vitro release.