论文部分内容阅读
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 develop Dang Ge Mingmu gel. Methods: Poloxamer 407 and 188 (P407, P488) were used as thermo-sensitive materials, and the uniform design method was used to optimize the formulation. The viscosity of the gel was investigated. The dissolution mechanism of the drug was studied in vitro. Of eye irritation were evaluated; the gel retention time in the eye was observed by fluorescence tracer method. Results: The gel temperature of ophthalmic temperature-sensitive gel increased with the increase of P407 concentration, and the gelation temperature decreased gradually. With the increase of P188 concentration, the gelation temperature increased gradually and the effect of P407 on gelation temperature was greater than P188. Uniform design method to optimize the best prescription for the 19% P407 and 1% P188 combined, based on the concentration of the preparation of Dange Mingmu gel that is free-flowing liquid below 26.9 ℃, at the same time diluted by tear in 34.5 ℃ can change phase to form a gel. Drug release in vitro showed zero-order kinetic characteristics, the amount of release depends on the amount of gel dissolution. Eye retention times indicate that the gel remains in the eye for longer periods of time, while animal experiments show gel eye irritation. Conclusion: The uniform design method can be used for ophthalmic thermosensitive gel prescription optimization. The prepared Dang Ge Mingmu gel is in line with the design requirements of ophthalmic medication and is expected to be applied clinically.