Corneal sequestration and delivery to ciliary process of six topically applied sulfonamides

The accession to cornea, aqueous humor and ultimately ciliary process was studied for a series of 6 sulfonamides which differed in their free acid lipophilicities. The drugs were applied as 5 mM solutions at pH 5 in unionized form or in chiefly ionized form at pH 8.4-9.4. These latter solutions contained 10% unionized drug. At 30 minutes post dose corneal drug levels were 2-3 fold higher for ionized compared to unionized application for a given drug. For ionized application there was a direct correlation between corneal drug accumulation and the lipophilicity of the unionized form of the drug. Cornea and aqueous humor drug levels were nearly equal 30 minutes following unionized application but significantly higher in cornea compared to aqueous humor after ionized application, suggesting drug was being retained in the cornea in ionized form. The efficiency of drug accession to ciliary process from cornea was assessed for the different drugs. The greatest accession to ciliary process from cornea as measured by the ratio of the two drug levels was found to correspond to compounds with free acid CHCl3/buffer partition coefficients approximately equal to unity. These results are discussed in terms of possible pathways of drug diffusion in the eye and the known intraocular pressure effects of topically applied sulfonamides.