PILOCARPINE INCORPORATED INTO A SUBMICRON EMULSION VEHICLE CAUSES AN UNEXPECTEDLY PROLONGED OCULAR HYPOTENSIVE EFFECT IN RABBITS

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 intra ocular pressure (IOP) was studied following a single dose application in normotensive rabbits. Membrane filtration (steam autoclaving) was f ound not to affect particle size distribution, zeta potential or pH of the pilocarpine emulsion preparation. A single dose application of pi locarpine emulsion 1.7% (equivalent to 2% pilocarpine hydrochloride) i nduced a prolonged progressive decrease in IOP in normotensive rabbits , which started at eleven hours post instillation and reached its maxi mal value of 6.0+/-0.2 mmHg at 29 hours. The pressure decreasing effec t induced by pilocarpine emulsion treatment followed a pattern differe nt from that generated by generic pilocarpine (Pilocarpine Hydrochlori de 2% eye drops); In the latter group, IOP reduction (starting at two hours) persisted during the initial five hours past instillation, whil e in the former, the hypotensive effect started at a later stage, and was maintained during a twenty nine hour follow-up causing a greater I OP decrease than in the generic group (%Delta IOP of 28.5% and 18%, re spectively). In the contralateral eyes of Pilocarpine Emulsion treated rabbits, an ocular hypotensive effect was noted late after applicatio n (11 hours through 29 hours post-instillation), while this effect was negligible in rabbits - treated with aqueous pilocarpine. Our finding s point to the possibility that the novel preparation of pilocarpine i ncorporated 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 pr eparation.