Different effects of absorption promoters on corneal and conjunctival penetration of ophthalmic beta-blockers.
OBJECTIVE
The purpose of this study was to investigate the improvement in corneal penetration of ophthalmic beta-blockers of various lipophilicities afforded by absorption promoters and to compare the corneal against conjunctival penetration in response to absorption promoters.


METHODS
The penetration of the beta-blockers, atenolol, carteolol, tilisolol, timolol, and befunolol, in the presence of absorption promoters, across the isolated corneal and conjunctival membranes of albino rabbits was measured using a two-chamber glass diffusion cell. EDTA, taurocholic acid, capric acid, and saponin were used as the absorption promoters.


RESULTS
The absorption promoters significantly increased the corneal permeability of most beta-blockers, especially the hydrophilic agents. The absorption promoters also enhanced the conjunctival permeability of beta-blockers, although their effect in promoting conjunctival penetration was less than that on corneal penetration. There was a differing penetration of instilled beta-blockers in the cornea and conjunctiva in response to absorption promoters. Capric acid and saponin showed significant promoting action on corneal penetration, but not on conjunctival penetration. Taurocholic acid had a significant effect on conjunctival penetration but not on corneal penetration. Saponin caused slight irritation.


CONCLUSIONS
Absorption promoters can improve the ocular delivery of beta-blockers and a selective use of absorption promoter can improve the extent and pathway of drug ocular absorption.
D000042:Absorption; D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D001767:Blinking / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism*; D003315:Cornea / Q000187:drug effects / Q000378:metabolism*; D005079:Excipients / Q000494:pharmacology*; D066298:In Vitro Techniques; D007509:Irritants / Q000633:toxicity; D008297:Male; D011817:Rabbits
D000319:Adrenergic beta-Antagonists; D005079:Excipients; D007509:Irritants