OCULAR MEMBRANE-PERMEABILITY OF HYDROPHILIC DRUGS FOR OCULAR PEPTIDE DELIVERY

The purpose of this study is to investigate the ocular membrane permea bility and the permeation mechanism of hydrophilic drugs such as thyro tropin-releasing hormone (TRH), p-nitrophenyl beta-cellopentaoside (PN P) and luteinizing hormone-releasing hormone (LHRH). The penetration o f hydrophilic drugs was measured across the isolated corneal and conju nctival membranes of albino rabbits using a two-chamber diffusion glas s cell. The corneal permeabilities of hydrophilic drugs were much lowe r than those of beta blockers reported previously. The corneal penetra tion of TRH was the highest among the hydrophilic drugs studied. Scrap ing the corneal epithelium increased the penetration of hydrophilic dr ugs. Conjunctival membranes showed higher permeability to hydrophilic drugs compared with corneal membranes. The permeability of drugs was a lso analysed by Fick's equation. The partition parameter and diffusion parameter of TRH, PNP and LHRH in the cornea were lower than those in scraped cornea and conjunctiva. In addition to the data of fluorescei n isothiocyanate-dextran reported previously, the permeability coeffic ient of hydrophilic drugs through the cornea, scraped cornea and conju nctiva correlated with molecular weight of the drugs. The diffusion pa rameters of hydrophilic drugs decreased with an increase of molecular weight for all ocular membranes. The extent of dependency of partition parameters on the molecular weights of drugs varied according to the ocular membrane. These results indicate that ocular membranes are suff iciently different in permeation character and mechanism to control th e extent and pathway for ocular absorption of hydrophilic drugs.