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目的:制备盐酸氮卓斯汀温敏型原位凝胶滴眼液。方法:以泊洛沙姆407、泊洛沙姆188和羟丙基甲基纤维素为辅料,冷溶法制备盐酸氮卓斯汀温敏型原位凝胶滴眼液;试管倒转法测定胶凝温度,星点设计-响应面法设计试验,泊洛沙姆407、188和羟丙甲纤维素为自变量,凝胶被模拟泪液稀释前后的胶凝温度(T_1,T_2)为因变量,拟合方程及方差分析,优化处方,预测值和实测值比较分析。结果:泊洛沙姆407和188的浓度显著影响胶凝温度,泊洛沙姆407浓度和胶凝温度呈负相关,泊洛沙姆188浓度和胶凝温度正相关,羟丙甲纤维素降低胶凝温度较小,模拟泪液稀释使胶凝温度升高较大。T1和T2二元多项式方程代表性较好,模型方差分析差异显著,而自变量交叉方差分析不显著。P407 22.00%-P188 4.50%-HPMC 0.25%,P407 21.44%-P188 3.35%-HPMC 0.20%,P407 21.07%-P188 3.00%-HPMC 0.20%3个优选处方胶凝温度(T_1,T_2)预测值和实测值的偏差在±1%以内,满足室温下呈流动态、经模拟泪液稀释后32℃实现胶凝的基本要求。处方中盐酸氮卓斯汀含量为0.05%。结论:通过星点设计-响应面法实现了盐酸氮卓斯汀温敏型原位凝胶滴眼液处方优化,制备了盐酸氮卓斯汀温敏型原位凝胶滴眼剂,为盐酸氮卓斯汀的临床应用提供了一种新的制剂研究。
Objective: To prepare azelastine hydrochloride thermosensitive in situ gel eyedrops. Methods: Poloxamer 407, poloxamer 188 and hydroxypropyl methylcellulose were used as excipients to prepare azelastine thermosensitive in situ gel drop solution by cold-dissolving method. Coagulation temperature and star point design-response surface design test, Poloxamer 407,188 and hypromellose were used as independent variables. The gelation temperature (T_1, T_2) before and after dilution of the gel was simulated as the dependent variable, Fitting equation and analysis of variance, optimization of prescription, prediction and comparison of measured values. Results: The concentrations of poloxamer 407 and 188 significantly affected the gelling temperature. The concentration of poloxamer 407 was negatively correlated with the gelling temperature. The concentration of poloxamer 188 was positively correlated with the gelation temperature, while hypromellose was decreased Gelation temperature is small, simulated tear dilution to gelation temperature greater. T1 and T2 bivariate polynomial equation representation is good, the model variance analysis significant difference, and independent variables cross-variance analysis is not significant. P407 22.00% -P188 4.50% -HPMC 0.25%, P407 21.44% -P188 3.35% -HPMC 0.20%, P407 21.07% -P188 3.00% -HPMC 0.20% The predicted value of the three preferred pregelatinized gelling temperature (T_1, T_2) Deviations of the measured values within ± 1%, to meet the room temperature was dynamic, diluted by simulated tears after 32 ℃ to achieve the basic requirements of gelation. The prescription of azelastine hydrochloride content of 0.05%. CONCLUSIONS: The azeotrope-based in situ gel in situ eyedrops formulation was optimized by the method of star point design-response surface method. Azelastine hydrochloride in situ gel eyedrops was prepared for hydrochloric acid The clinical application of azelastine provides a new formulation study.