Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui Province 230012, People's Republic of China.
Department of Pharmaceutics, College of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui Province 230012, People's Republic of China; Institute of Pharmaceutics, Anhui Academy of Chinese Medicine, Hefei, Anhui Province 230012, People's Republic of China.
Int J Pharm. 2019 May 1;562:31-41. doi: 10.1016/j.ijpharm.2019.02.033. Epub 2019 Mar 14.
The aim of this paper was to develop hexagonal liquid crystalline (H) gels that can be used as a novel ocular delivery system for pilocarpine nitrate (PN). H gels were prepared by a vortex method using phytantriol/triglyceride/water (71.15: 3.85: 26, w/w) ternary system. The gels were characterized by crossed polarized light microscopy, small-angle X-ray scattering, differential scanning calorimetry and rheology. And, in vitro drug release behavior and ex vivo corneal permeation were investigated. Finally, preocular residence time evaluation, eye irritation test, histological examination and miotic tests were studied in vivo and compared with carbopol gel. Based on various characterization techniques, the inner structure of the gels were H mesophase and exhibited a pseudoplastic fluid behaviour. In vitro release results revealed that PN could be released continuously from H gel over a period of 24 h. The ex vivo apparent permeability coefficient of H gel was 3.15-fold (P < 0.01) higher than that of the Carbopol gel. Compared with Carbopol gel, H gel displayed longer residence time on the eyeballs surface using fluorescent labeling technology. Furthermore, the H gel caused no ocular irritation was estimated by corneal hydration levels, Draize test and histological inspection. Additionally, in vivo miotic study showed that H gel had a remarkably long-lasting decrease in the pupil diameter of rabbits. In conclusion, H gels would be a promising sustained-release formulation for ocular drug delivery.
本文旨在开发可用于硝酸毛果芸香碱（PN）眼部递药的新型六角液晶（H）凝胶。采用涡旋法，利用植物三醇/甘油三酯/水（71.15:3.85:26，w/w）三元体系制备 H 凝胶。采用偏光显微镜、小角 X 射线散射、差示扫描量热法和流变学对凝胶进行了表征。并考察了体外释药行为和离体角膜渗透。最后，进行了预眼停留时间评价、眼刺激性试验、组织学检查和缩瞳试验的体内研究，并与卡波姆凝胶进行了比较。基于各种表征技术，凝胶的内部结构为 H 中间相，表现出假塑性流体行为。体外释放结果表明，PN 可在 24 h 内从 H 凝胶中持续释放。H 凝胶的体外表观渗透系数是卡波姆凝胶的 3.15 倍（P<0.01）。与卡波姆凝胶相比，荧光标记技术显示 H 凝胶在眼球表面的停留时间更长。此外，通过角膜水化水平、Draize 试验和组织学检查评估 H 凝胶无眼部刺激性。另外，体内缩瞳研究表明，H 凝胶可使兔瞳孔直径明显持久缩小。综上所述，H 凝胶有望成为眼部给药的一种新型缓控释制剂。
