METHYLPREDNISOLONE ESTERS OF HYALURONIC-ACID IN OPHTHALMIC DRUG DELIVERY - INVITRO AND INVIVO RELEASE STUDIES

Films and microspheres were prepared from various esters of hyaluronic acid. A model drug, methylprednisolone, was either physically incorporated into the polymer matrix or chemically bound to the polymer backbone through an ester linkage. In vitro release from films with covalently bound drug was much slower t50% = 71 h) than that for physically dispersed drug (t50% = 2.5-17 h). Methylprednisolone concentrations in the tear fluid of New Zealand rabbits were measured after ocular application of drug (approx. 420-mu-g) in different dosage forms. When methylprednisolone was physically dispersed in the polymer matrix, in vivo drug release from matrices was slower than that observed in vitro. Compared with a suspension control, peak methylprednisolone concentrations in tear fluid were 9-14 times lower after administration of drug in polymer films and AUC0-8 h values were 4.7 times higher. These results imply that hyaluronic acid ester preparations can increase the residence time of methylprednisolone in the tear fluid of rabbits.