Ocular tolerance of absorption enhancers in ophthalmic preparations.
The use of absorption promoters is a way to improve the bioavailability and therapeutic response of topically applied ophthalmic drugs. The ocular tolerance of 9 potential absorption promoters was investigated as well as the influence of the enhancers' concentration on the ocular tolerance. The substances tested were instillated repetitively (4 times per day, during 3 days, and once just before examination) as aqueous solutions onto rabbit corneas. Fluorescein dyeing enabled us to specifically mark corneal damage that was observed by confocal microscopy. The degree of corneal injury was assessed with an image-processing system that calculated the total fluorescent areas. Confocal microscopy results showed the relatively good tolerance of permeation enhancers like dimethyl sulfoxide (DMSO), decamethonium, edetate, glycocholate, and cholate in contrast to the poorly tolerated saponin and fusidate. Increasing the promoters' concentration led generally to an increase in corneal lesions.
Furrer
Pascal
P
School of Pharmacy, Institute of Medicinal Chemistry; University of Lausanne, CH-1015 Lausanne, Switzerland.
Mayer
Joachim Michael
JM
Plazonnet
Bernard
B
Gurny
Robert
R
D000042:Absorption / Q000187:drug effects; D000818:Animals; D001682:Biological Availability; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D005079:Excipients / Q000009:adverse effects*; D005260:Female; D008297:Male; D018613:Microscopy, Confocal; D009883:Ophthalmic Solutions / Q000009:adverse effects / Q000493:pharmacokinetics*; D011817:Rabbits
D005079:Excipients; D009883:Ophthalmic Solutions