EFFECTS OF 4 PENETRATION ENHANCERS ON CORNEAL PERMEABILITY OF DRUGS IN-VITRO

The usefulness of penetration enhancers in promoting drug permeation a cross the cornea was investigated for drugs varying from hydrophilic t o lipophilic. Four purported penetration enhancers [Azone (laurocapram ), hexamethylenelauramide, hexamethyleneoctanamide, and decylmethylsul foxide] were employed. Corneal permeability coefficients of drugs that were either hydrophilic (acetazolamide, cimetidine, guanethidine, and sulfacetamide), moderately lipophilic (bunolol and prednisolone), or lipophilic (flurbiprofen and its amide analogue) were measured in the absence or in the presence of various Atone concentrations. The effect s of penetration enhancers on the corneal penetration of cimetidine we re also compared. The corneal penetration of hydrophilic compounds was enhanced by at least 20-fold at 0.1 % Azone. For prednisolone and bun olol, the maximal enhancement was at 0.025-0.1% Atone and was marginal (two- to 5-fold), whereas Azone inhibited rather than enhanced the co rneal penetration of the lipophilic flurbiprofen and its amide analogu e. All four enhancers behaved similarly in enhancing corneal penetrati on of cimetidine and corneal hydration after incubation in vitro. Poss ible mechanisms of penetration enhancers on corneal drug penetration w ere discussed. Penetration enhancers may have clinical benefits in imp roving ocular drug delivery of hydrophilic compounds, however, their u tility may depend on the toxicological profiles.