Comparison of ion-activated in situ gelling systems for ocular drug delivery. Part 2: Precorneal retention and in vivo pharmacodynamic study.

In situ gelling systems are viscous polymer-based solutions that exhibit a sol-to-gel phase transition upon change in a physicochemical parameter such as ionic strength, temperature or pH, therefore prolonging the formulations' residence time on the ocular surface. Ion-activated in situ gelling systems, that are able to crosslink with the cations in the tear fluid, have previously been evaluated in terms of their rheological, textural and in vitro release characteristics. The present study describes the ocular irritancy, precorneal retention time and in vivo release characteristics of the same formulations. It was shown that all tested polymer systems were non-irritant. Precorneal retention studies revealed a biphasic rapid release for the solution with less than 40% radioactivity left on the ocular surface after 15 min, while formulations based on gellan gum, xanthan gum and carrageenan seemed to drain at an almost constant rate with more than 80% radioactivity remaining. This was in agreement with the in vivo miotic studies, which demonstrated that the area under the curve and the miotic response at 120 min after administration for gellan gum, xanthan gum and carrageenan formulations of pilocarpine were increased by 2.5-fold compared to an aqueous solution, which demonstrates their potential use in ophthalmic formulations.