星点设计-响应面法优化盐酸氮斯汀温敏型原位凝胶滴鼻剂处方

Optimization of the Formulation of Azelastine Hydrochloride Thermosensitive In-situ Gel Nasal Drops by Central Composite Design-Response Surface Methodology

目的:优化盐酸氮斯汀(AH)温敏型原位凝胶滴鼻剂处方。方法:以泊洛沙姆407(P407)、泊洛沙姆188(P188)为辅料,采用冷溶法制备AH温敏型原位凝胶。以P407、P188处方中的用量(g/100 ml)为因素,以相变温度为指标,采用星点设计-响应面法优化处方,进行二项式拟合,同时分析预测值和实测值偏差。结果:二项式拟合复相关系数R2=0.986 5;最优处方为P407占20.414 4%、P188占5.035 4%;3次验证试验的相变温度实测值为(30.81±0.02)℃,预测值为31℃,偏差为0.61%。结论:星点设计-响应面法可用于优化AH温敏型原位凝胶滴鼻剂处方。

OBJECTIVE：To optimize Azelastine hydrochloride（AH） thermosensitive in-situ gel nasal drops formulation.METHODS：Using poloxamer 407（P407）and poloxamer 188（P188）as excipients,AH thermosensitive in-situ gel was prepared by cold solution method. The formulation was optimized by central composite design-response surface methodology using the amount of P407 and P188（g/100 ml）as factors and phase-transition temperature as index. Binomial expression was fitted,and predicted and measured values were compared. RESULTS：The correlation coefficient R2 fitted by binomial expression was equal to0.986 5. The optimal formulation was as follows as P407 for 20.414 4%,P188 for 5.035 4%,measured value of（30.81±0.02）℃,predicted values of 31 ℃,deviation of 0.61%. CONCLUSIONS：AH thermosensitive in-situ gel nasal drops formulation is optimized by central composite design-response surface methodology.