盐酸莫西沙星温度敏感眼用凝胶的制备及体外释放

Preparation of Ophthalmic Thermosensitive in Situ Gel of Moxifloxacin Hydrochloride and Its Release Behavior in Vitro

目的研制盐酸莫西沙星温度敏感眼用凝胶,并考察其体外释放行为。方法采用冷溶法制备温敏凝胶;以泊洛沙姆407(P407)和泊洛沙姆188(P188)为温敏凝胶材料,模拟泪液稀释前后的胶凝温度为评价指标,采用均匀设计法对盐酸莫西沙星温度敏感眼用凝胶处方进行优化;采用无膜溶出法研究盐酸莫西沙星眼用凝胶的释药特性。结果盐酸莫西沙星温度敏感眼用凝胶的胶凝温度随P407浓度增大而降低,随P188浓度增加先升高后降低;模拟泪液的稀释可使胶凝温度升高;均匀设计法筛选出温度敏感眼用凝胶的最佳处方为230 mg·mL-1P407和80 mg·mL-1P188;凝胶溶蚀与药物的释放呈良好的相关性,说明眼用凝胶中药物的释放由凝胶的溶蚀所决定。结论均匀设计法可用于筛选眼用凝胶的处方,处方中含230 mg·mL-1P407和80 mg·mL-1P188的盐酸莫西沙星温度敏感眼用凝胶的性质满足眼部用药的设计要求,体现出良好的应用前景,可进一步研究开发。

OBJECTIVE To prepare moxifloxacin hydrochloride （MH）-loaded ophthalmic thermosensitive in situ gel and investi- gate its release behavior in vitro. METHODS Cold-dissolve method was used to prepare thermosensitive gel. The effects of two inde- pendent variables, poloxamer 407 and poloxamer 188, were evaluated. Uniform design method was used to optimize the formulation of MH-loaded ophthalmic thermosensitive gel as a function of before and after simulated tear fluid dilution. The in vitro release of MH from the optimized formulation gel was investigated by non-film stripping method. RESULTS The gelation temperature decreased with in- creasing of P407 concentration, and increased gradually then decreased with increasing of P188. The gelation temperature increased about 3 -5℃ after simulated tear fluid dilution. Uniform design method provided the best formulation： 230 mg· mL- 1 P407 and 80 mg· mL-1 P188. The MH release was determined by the gel diffusion. CONCLUSION Uniform design method should be used to optimize the formulation of MH loaded ophthalmic thermosensitive gel. The optimized formulation containing 230 mg · mL-1 P407 and 80 mg· mL- 1 P188 covered the ophthalmic temperature, which can serve as a potential candidate for ophthalmic application.