丹参川芎嗪鼻用温敏凝胶的制备及黏膜渗透性考察

Preparation of Salviae Miltiorrhiza and Ligustrazine Hydrochloride Nasal Thermosensitive in Situ Gel and Study on Characterization of Its Nasal Mucosal Permeability

目的:研制丹参川芎嗪鼻用温敏凝胶并对其体外释放度及粘膜渗透性进行考察。方法:以泊洛沙姆407(P407)、泊洛沙姆188(P188)、PEG-6000的用量为考察因素,胶凝温度为考察指标,通过星点设计-效应面法优选丹参川芎嗪温敏凝胶基质处方;采用Franz扩散池法考察该制剂体外释放和黏膜渗透作用。结果:最优处方中P407、P188、PEG-6000用量分别为18%、7%、1%,载药凝胶中药物12 h累积释放度为70%以上,释放曲线符合一级动力学方程。载药凝胶中盐酸川芎嗪和丹参素12 h累积渗透量分别为2 649.77和119.72μg/cm2。结论:星点设计-效应面法所建模型能较好地应用于该凝胶的处方优化,同时研制的凝胶制剂具有胶凝温度准确、缓释和较好的黏膜渗透作用。

Objective： To prepare the salviae miltiorrhiza and ligustrazine hydrochloride nasal thermosensitive in situ gel and to study the characterization of its nasal mucosal permeability. Methods： With gelling temperature as the dependent variable,the contents of poloxamer 407（ P407）,poloxamer 188（ P188） and PEG-6000 as independent variables. The best prescription was optimized by central composite design-response surface methodology. The release in vitro and the skin permeation ability were evaluated in Franz diffusion cell. Results： The optimal formulation composed with the dosage of P407,P188 and PEG-6000 were 18%,7% and 1%,respectively. The cumulative release in vitro was over 70% after 12 h,and the release curve conformed to the first-order kinetic equation. The cumulative permeation of salviae miltiorrhiza and ligustrazine hydrochloride in the gel were 2 649. 77 μg / cm2 and 119. 72 μg / cm2 after 12h. Conclusion： The central composite design-response surface methodolog was stable and feasible for preparation of nasal thermosensitive in situ gel of salviae miltiorrhiza and ligustrazine hydrochloride,the drug-loaded gel has sustained release effect.