基于眼部特点的麝丹即型凝胶的制备与评价

Preparation and evaluation of Shedan in situ forming gel based on ocular characteristics

该实验采用中心组合设计-效应面法制备并优化了温敏型麝丹眼用即型凝胶,其处方最佳基质为18%的泊洛沙姆407(P407)和5%的泊洛沙姆188(P188);应用安东帕MCR302流变仪对其进行了流变学考察,振幅扫描结果显示应控制其应变(γ)<0.5%,在高频区其弹性模量(G')大于黏性模量(G″),表现为凝胶特征,有较好的稳定性,通过温度扫描G',G″及相角(δ)的变化来确定了其相变温度(TSG)为33.25℃,触变性实验显示其结构恢复时间短于5 s;分别采用表面张力仪、露点渗透压仪分别测定了其表面张力和渗透压,结果分别为36.43 m N·m-1,320.6 m Osm·kg-1;荧光标记示踪法观察了其在眼角膜的滞留时间为180 min;其溶出实验表现为零级释放动力学特征,麝香酮和丹酚酸B的释放与药物溶蚀线性相关;眼部刺激性实验显示其无刺激性。麝丹即型凝胶有望为临床视网膜静脉阻塞治疗提供一种新型外用长效制剂。

To develop an ophthalmic preparation of Shedan,an in situ forming gel was prepared with the formulation containing18% of poloxamer 407 and 5% of poloxamer 188 by response surface designs plus central composite designs. The rheology results showed that LVE range gamma should limited within 0. 5%,Shedan high-frequency region,and the thixotropy recovery time is less than 5 seconds. The phase transition temperature was 33. 25 ℃ according to curve of storage modulus and loss modulus determined by temperature scanning. Surface tension and osmometer of it determined by surface tension meter and dew point osmometer were 36. 43 m N·m-1,and 320. 6 m Osm·kg-1,respectively. Fluorescein sodium was selected as the marker to monitor the corneal residence time,and the results showed that Shedan gel could prolong drug residence for 180 min. In line with zero-order kinetics,releases of muscone and salvianolic acid B in vitro depends on gels erosion. The results of rabbit ocular irritation experiments suggested that Shedan in situ forming gel was biocompatible and nonirritant. In conclusion,a novel Shedan in situ forming gel was developed and characterized for potential drug treatment of retinal vein occlusion.