叶黄素眼用温敏型原位凝胶的制备及体外释放研究

Preparation of Lutein Thermosensitive in Situ Gels for Ophthalmic Use and the in Vitro Release

目的采用星点设计-效应面法优化叶黄素温敏凝胶处方,并对其体外释放行为进行考察。方法以胶凝温度为评价指标,考察泊洛沙姆407(P407)和泊洛沙姆188(P188)用量对胶凝温度的影响,使用星点设计-效应面法进行优化,再通过无膜溶出法考察凝胶溶蚀及药物释放。结果 P407及P188用量两个影响因素与胶凝温度之间存在定量关系,最佳处方:P407质量浓度为0.21 g·m L-1,P188质量浓度为0.03 g·m L-1,凝胶溶蚀及药物释放符合零级动力学方程。结论所建立的模型预测性良好,可用于叶黄素原位凝胶处方的预测及优化。

OBJECTIVE To optimize the formulation of the lutein thermosensitive in situ gels by using central composite design- response surface methodology, and study the drug release in vitro. METHODS Gelation temperature was served as the indicator. The influences of the amounts of Poloxamer 407 and Poloxamer 188 on the gelation temperature were investigated. Central composite design- response surface method was used to optimize the prescription. The drug release profile of the preparation was investigated with a mem- brane-less dissolution model. RESULTS The amounts of Poloxamer 407 and Poloxamer 188 had quantitative relationships with the gelation temperature. The optimum prescription was as follows： the mass concentration of P407 was 0. 21 g·mL^-1, and the mass con- centration of P188 was 0. 03 g · mL^-1. The dissolution and drug release of the gels followed zero-order kinetics equation. CONCLU- SION Central composite design-response surface methodology can be applied to optimize the formulation of the lutein thermosensitive in situ gels.