Preparation and evaluation of ophthalmic pH sensitive in-situ gel of acyclovir

LI Xin-ru; LEI Yao-long; SHEN Chuan-yong; ZHOU Yan-xia; CHEN Xing-wei; LIU Yan

doi:10.3321/j.issn:1003-3734.2009.24.019

Abstract：Objective: To prepare acyclovir (ACV) pH sensitive in-situ gel and evaluate its behavior in vitro. Methods: Rheological quality was investigated by effect of pH and temperature on viscosity of in-situ gel. Ocu-lar residence time was determined by Fluorescence-labeled technique. Ocular safety was evaluated by ocular irrita-tion test in rabbit according to Guiding Principles for Stimulation, Allergy and Hemolysis of New Drug. The cornea permeation test of ACV pH sensitive in-situ gel was studied using Franz diffusion cell with rabbit corneas. The per-meation amount of ACV was determined by high performance liquid chromatography. Results: The rheological curve demonstrated that the ACV pH sensitive in-situ gel represented pseudoplastic flow type. Both ACV pH sensitive in-situ gel and ACV eye-drop had no irritation after ocular administration. The ocular residence time of ACV pH sensi-tive in-situ gel (22. 4 ± 1. 4 min ) were as 5. 6 times as that of ACV eye-drop (4.0 ± 0.5 min ). The perfusion through the isolated rabbit cornea demonstrated that the drug concentration of aqueous humour for ACV in-situ gel was higher than that for eye drop after 0. 25 h of ocular administration and the cornea acted as drug reservoir at some extent. Conclusion: As a liquid ophthalmic delivery systems, ACV pH sensitive in-situ gel could undergo in-si-tu phase transition to form gels which decreased drug release rate,and showed characteristics of sustained release.