Effects of four penetration enhancers on corneal permeability of drugs in vitro.

The usefulness of penetration enhancers in promoting drug permeation across the cornea was investigated for drugs varying from hydrophilic to lipophilic. Four purported penetration enhancers [Azone (laurocapram), hexamethylenelauramide, hexamethyleneoctanamide, and decylmethylsulfoxide] 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 Azone concentrations. The effects of penetration enhancers on the corneal penetration of cimetidine were also compared. The corneal penetration of hydrophilic compounds was enhanced by at least 20-fold at 0.1% Azone. For prednisolone and bunolol, the maximal enhancement was at 0.025-0.1% Azone and was marginal (two- to 5-fold), whereas Azone inhibited rather than enhanced the corneal penetration of the lipophilic flurbiprofen and its amide analogue. All four enhancers behaved similarly in enhancing corneal penetration of cimetidine and corneal hydration after incubation in vitro. Possible mechanisms of penetration enhancers on corneal drug penetration were discussed. Penetration enhancers may have clinical benefits in improving ocular drug delivery of hydrophilic compounds, however, their utility may depend on the toxicological profiles.