丹葛明目即型凝胶的制备研究

Study on preparation of Dange Mingmu in-situ forming eye gel

目的:研制丹葛明目即型凝胶。方法:以泊洛沙姆407和188(P407,P488)为温敏材料,采用均匀设计法优化处方,考察了凝胶的黏度;采用无膜溶出模型对药物的体外释放机制进行研究;对制剂的眼刺激性进行评价;采用荧光示踪法观察了凝胶在眼部的滞留时间。结果:眼用温度敏感型凝胶温度随P407浓度的增大,胶凝温度逐渐降低,在一定范围内随着P188浓度的增加,胶凝温度逐渐升高,且P407对胶凝温度的影响大于P188。均匀设计法优化得最佳处方为19%P407与1%P188合用,在此基础上调整浓度制备的丹葛明目即型凝胶在26.9℃以下为自由流动的液体,同时被泪液稀释后在34.5℃能发生相变形成凝胶。药物的体外释放呈零级动力学特征,释放量取决于凝胶溶蚀量。眼部滞留时间表明凝胶在眼部可较长时间保留,同时动物试验表明凝胶眼部无刺激性。结论:均匀设计法可用于眼用温敏凝胶处方的优化,所制备的丹葛明目即型凝胶符合眼部用药的设计要求,有望在临床中获得应用。

Objective: To prepare Dange Mingmu in-situ forming eye gel.Method: The viscosity of Dange Mingmu in-situ forming eye gel was tested by adopting poloxamer 407 and 188 as thermosensitive materials,and optimizing by uniform design.Drug release in vitro was studied using a novel membraneless model.Eye irritation experiments were performed with rabbits.The duration of residence time in rabbit eyes was observed using fluorescence tracer method.Result: The gelation temperature of in-situ thermosensitive gel was lowered as the P407 concentration increased.In a certain range,the gelation temperature slowly increased with the increase of P188's concentration,and the effect of P407 was greater than that of P188.The optimized concentration of P407/P188 was 19%/1%.Based the adjusted concentration,Dange Mingmu in-situ forming eye gel.was converted into freely flowing liquid below 26.9 ℃ and became gel at 34.5 ℃ after being diluted with STF.In line with zero-order kinetics,drug release in vitro depends on gel erosion.The residence time on the surface of eyes was proved to be relatively long was and nonirritant.Conclusion: Uniform design is available for optimizing the formulation of thermosensitive gel for eye.The gel satisfies the requirement for ophthalmic application,and is expected to be applied in clinical practice in the future.