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Corneal endothelial changes with azone, a penetration enhancer
G Durand-Cavagna1, P Duprat, S Molon-Noblot
1Merck Sharp & Dohme-Chibret Laboratories, Riom, France.
Lens and Eye Toxicity Research
|January 1, 1989
Summary
Azone at 1-2% in ophthalmic formulations caused ocular toxicity in rabbits, damaging corneal endothelial cells. Further research is needed to determine if Azone directly causes irritation or enhances penetration of other irritants.
Area of Science:
- Ophthalmology
- Pharmacology
- Toxicology
Background:
- Azone enhances percutaneous absorption, making it a potential ingredient in ophthalmic formulations.
- Its use could increase drug therapeutic action or allow lower active ingredient concentrations.
Purpose of the Study:
- To evaluate the ocular irritation potential of ophthalmic vehicles containing Azone in rabbits.
- To assess the safety of incorporating Azone into eye drop formulations.
Main Methods:
- Rabbits received topical ophthalmic vehicles with 0%, 1%, or 2% Azone three times daily for 29 days.
- Ocular irritation was assessed through clinical signs and histopathological examination.
- Corneal endothelial cell changes were analyzed using scanning electron microscopy and semi-thin sections.
Main Results:
- Ophthalmic vehicles with 1% and 2% Azone induced clinical and histopathological signs of ocular toxicity.
- Transient irritation included conjunctival and iris redness, discharge, and corneal edema.
- Corneal endothelial cells showed ballooning and vacuolation, distorting their typical appearance.
Conclusions:
- Instillation of ophthalmic vehicles containing 1% or 2% Azone damages rabbit corneal endothelial cells.
- The exact cause of irritation remains unclear: direct Azone toxicity or enhanced penetration of other formulation components like benzalkonium chloride.