Miotic effect and irritation potential of pilocarpine prodrug incorporated into a submicron emulsion vehicle.
Pilocarpine prodrug, O,O'-dipivaloyl(1,2-ethylene) bispilocarpic acid diester, was introduced to a submicron emulsion vehicle in a dose equivalent to 0.5% pilocarpine base, and the formulation was studied in albino rabbits using miotic assay. Compared with pilocarpine HCl 0.5% solution delayed and prolonged miosis was observed after application of the prodrug emulsion. AUC(0-6 h) values for the prodrug emulsion and pilocarpine solution were 9252+/-1345 and 6845+/-1967%xmin, respectively. The prodrug was also administered twice daily for 5 days in the form of aqueous solution or submicron emulsion in order to study ocular irritation. Irritation potential of the prodrug was significantly reduced when submicron emulsion was used as a vehicle.
Sznitowska
M
M
Department of Pharmaceutical Technology, Medical University of Gdansk, ul.Hallera 107, 80-416, Gdansk, Poland.
Zurowska-Pryczkowska
K
K
Janicki
S
S
Järvinen
T
T
D000818:Animals; D001682:Biological Availability; D004655:Emulsions; D007509:Irritants / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D008916:Miotics / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity*; D010316:Particle Size; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage* / Q000737:chemistry; D010862:Pilocarpine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity*; D011355:Prodrugs / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity*; D011817:Rabbits
D004655:Emulsions; D007509:Irritants; D008916:Miotics; C121851:O,O'-dipivaloyl (1,2-ethylene)bispilocarpic acid diester; D014677:Pharmaceutical Vehicles; D011355:Prodrugs; D010862:Pilocarpine