In vivo evaluation of submicron emulsions with pilocarpine: the effect of pH and chemical form of the drug

Submicron emulsions containing 2.0% w/v pilocarpine as pilocarpine HCl, soy bean oil (10% w/v) and egg lecithin (1.2% w/v) were formulated. Emulsions a t pH 5.0, 6.5 and 8.5 were applied to the rabbit's eye, and the reduction i n pupil diameter was measured for 6 h. The miotic effect was compared with that obtained with aqueous solutions at the same pH. A prolonged miotic eff ect was observed when the submicron emulsion was used as a vehicle. After a pplication of emulsions at pH 5.0, 6.5 or 8.5, the time when 20% reduction of pupil diameter was still observed was 3.9 +/- 1.1 h, 4.3 +/- 1.3 h and 5 .3 +/- 0.8 h, respectively, while, after application of a solution, this pa rameter was shorter by 30-40%. AUC(0-6h) values were larger after applicati on of the submicron emulsions in comparison to aqueous solutions; however, statistically significant differences were only observed for emulsions at p H 6.5. Although the bioavailability of the drug is pH dependent, emulsions at higher pH cannot be considered for clinical use because of pilocarpine d egradation which occurs with a similar rate as in aqueous solutions. Introd uction of pilocarpine into the oily phase in the form of pilocarpine base o r its oleate did not improve either the physicochemical or the pharmacologi cal properties of the formulations. Irrespective of the pH and chemical for m of pilocarpine used for emulsion preparation, practically all drug was fo und in the aqueous phase of the emulsion; thus, partitioning to the oily ph ase was negligible.