苄达赖氨酸温敏型眼用原位凝胶的体外释放性及角膜渗透性考察

Study on in Vitro Release and Corneal Permeation of a Thermoresponsive Ophthalmic in Situ Gel Containing Bendazac Lysine

关键词:  原位凝胶  眼  苄达赖氨酸  释放  渗透

Key words:  in situ gel  ocular  bendazac lysine  release  permeation

摘要:

目的 研究苄达赖氨酸温敏型眼用原位凝胶体外释放性及离体角膜渗透性。方法 考察泊洛沙姆P407及P188用量对处方凝胶温度的影响，并对结果进行二项式拟合筛选出最优处方；以市售滴眼液或溶液剂为对照，采用无膜法、透析袋法、透析膜法考察了该处方的体外释放性；采用Franz扩散池对该处方进行了离体角膜渗透研究。结果 该优选处方对角膜刺激性较小，胶凝温度为31.5 ℃，pH为6.95，渗透压为397 mOsmol·kg^-1；相比于对照组，该处方缓释效果明显，未出现突释效应；离体角膜渗透研究结果表明，该优选处方6 h角膜累积渗透率及渗透速率均低于市售处方。结论 温敏型原位凝胶缓释效果明显，有望成为治疗白内障药物苄达赖氨酸的新剂型。

Abstract:

OBJECTIVE To study the in vitro release and corneal permeation of a thermoresponsive ophthalmic in situ gel containing bendazac lysine. METHODS The effect of the concentration of Poloxamer407 and 188 on the gelation temperature was evaluated, then the results were fitted with second-order quadratic models to optimize the formulation. Using aqueous solution or eye drops as control, the in vitro release of the formulation was evaluated by membrane-less method, dialysis bag method and dialysis membrane method. Then, the corneal permeation experiment of the optimum formulation was carried out with Franz diffusion cells. RESULTS The optimium formulation had low corneal irritation, gelling temperature of 31.5 ℃, pH of 6.95, and osmotic pressure of 397 mOsmol·kg^-1. Compared to the control group, the optimum formulation had significant sustained release effect without burst release. The result of the corneal permeation showed that the corneal permeation rate of the in situ gel was lower than the eye drops. CONCLUSION With significant sustained release effect, the thermoresponsive ophthalmic in situ gel will become a promising alternative formulation for bendazac lysine which was used for treating cataract.