Effect of physical cross-linking on in vitro and ex vivo permeation of indomethacin from polyvinyl alcohol ocular inserts

Abstract

Polymeric ophthalmic inserts containing indomethacin were formulated with combinations of two different types of polyvinyl alcohol (high-1,25,000 and low-14,000 molecular weights) and physically reinforced by heating (80° and 100° for 24 and 48 h) and freeze-thawing (3 and 6 cycles). In vitro drug release and permeation kinetics across goat cornea was studied in a continuous flow-through apparatus and a modified Keshary-Chien cell, respectively, and compared with the non-reinforced inserts. The rate of indomethacin release was inversely proportional to low molecular weight polyvinyl alcohol content. The duration of heating had more effect on drug release than the temperature and freeze thawing was more successful in retarding the drug release. The permeation of indomethacin correlated well with the in vitro release.