Pilocarpine incorporated into a submicron emulsion vehicle causes an unexpectedly prolonged ocular hypotensive effect...

Pilocarpine, a widely used antiglaucoma drug, was incorporated into a newly developed submicron emulsion (pilocarpine emulsion) suitable for local ocular administration. Pilocarpine-Emulsion effect on the intraocular pressure (IOP) was studied following a single dose application in normotensive rabbits. Membrane filtration (steam autoclaving) was found not to affect particle size distribution, zeta potential or pH of the pilocarpine emulsion preparation. A single dose application of pilocarpine emulsion 1.7% (equivalent to 2% pilocarpine hydrochloride) induced a prolonged progressive decrease in IOP in normotensive rabbits, which started at eleven hours post instillation and reached its maximal value of 6.0 +/- 0.2 mmHg at 29 hours. The pressure decreasing effect induced by pilocarpine emulsion treatment followed a pattern different from that generated by generic pilocarpine (Pilocarpine Hydrochloride 2% eye drops); In the latter group, IOP reduction (starting at two hours) persisted during the initial five hours post-instillation, while in the former, the hypotensive effect started at a later stage, and was maintained during a twenty nine hour follow-up causing a greater IOP decrease than in the generic group (% delta IOP of 28.5% and 18%, respectively). In the contralateral eyes of Pilocarpine Emulsion treated rabbits, an ocular hypotensive effect was noted late after application (11 hours through 29 hours post-instillation), while this effect was negligible in rabbits-treated with aqueous pilocarpine. Our findings point to the possibility that the novel preparation of pilocarpine incorporated into submicron emulsion might serve as a long-acting form of pilocarpine which might require a single daily application. Further studies are required to elucidate the mechanism and action of this preparation.