M. Sznitowska et al., In vivo evaluation of submicron emulsions with pilocarpine: the effect of pH and chemical form of the drug, J MICROENC, 18(2), 2001, pp. 173-181
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.