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.
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.
Authors: Giselle Foureaux; Juçara Ribeiro Franca; José Carlos Nogueira; Gustavo de Oliveira Fulgêncio; Tatiana Gomes Ribeiro; Rachel Oliveira Castilho; Maria Irene Yoshida; Leonardo Lima Fuscaldi; Simone Odília Antunes Fernandes; Valbert Nascimento Cardoso; Sebastião Cronemberger; André Augusto Gomes Faraco; Anderson José Ferreira Journal: PLoS One Date: 2015-07-23 Impact factor: 3.240
Authors: Ratnakar Tripathi; Praveen K Balne; Nishant R Sinha; Lynn M Martin; Sabeeh Kamil; James R Landreneau; Suneel Gupta; Jason T Rodier; Prashant R Sinha; Nathan P Hesemann; Alexandria C Hofmann; Michael K Fink; Shyam S Chaurasia; Rajiv R Mohan Journal: Transl Vis Sci Technol Date: 2020-11-02 Impact factor: 3.283