Purpose: This study aimed to develop low-viscosity aqueous eyedrops containing enalaprilat and its prodrug enalapril maleate in solution, and to evaluate the eyedrops in rabbits.
Methods: Aqueous eyedrops with hydroxypropyl-beta-cyclodextrin containing 0.01-2.9% (w/v) enalaprilat, 1.0% (w/v) enalapril maleate with cyclodextrin or 0.5% (w/v) timolol were prepared. The eyedrops were administered to rabbits and intraocular pressure (IOP) was measured at various time intervals after the administration and the results (mean of 10 experiments +/- standard error of the mean) are expressed as the change from baseline (24.7 +/- 3.3 mmHg).
Results: Enalaprilat possessed sufficient stability to be formulated as an aqueous eyedrop solution with a shelf-life of several years at room temperature. The maximum decline in IOP after topical administration of one drop of 2.9% enalaprilat solution was 6.2 +/- 0.7 mmHg at 4 hours after administration. Duration of activity exceeded 10 hours. A 1% enalaprilat solution lowered IOP by 4.4 +/- 0.8 mmHg at 4 hours after administration and had similar duration, and was more potent than 0.5% timolol. The enalapril maleate eyedrops resulted in delayed action, showing maximum potency at 10-22 hours after administration and duration of up to 32 hours.
Conclusions: Enalaprilat eyedrops lower IOP in rabbits. The decline in IOP is proportional to the concentration of dissolved enalaprilat in low-viscosity aqueous eyedrop formulations.