Concomitant and controlled release of dexamethasone and 5-fluorouracil from poly(ortho ester)

A Viscous bioerodible and hydrophobic poly(ortho ester) has been developed as a biocompatible, sustained drug release system for an ophthalmic applica tion in intraocular proliferative disorders. The combination of wound heali ng modulators such as 5-fluorouracil and dexamethasone is a major advantage since these drugs act at different stages of these diseases. Since 5-fluor ouracil is an acidic, water-soluble compound and dexamethasone exists in th ree chemical forms, i.e. the water-insoluble base, the highly hydrophobic a cetate ester or the basic phosphate salt, it was of interest to investigate whether the physicochemical properties of the drugs have an influence on t heir release rates, and whether a concomitant and sustained release of both 5-fluorouracil and dexamethasone could be achieved. It has been found that lipophilicity and acidobasicity play a major role in controlling drug rele ase rates and polymer degradation. The combination of 5-fluorouracil and de xamethasone phosphate allows a sustained and concomitant release of both dr ugs, due to the basic characteristics of the corticosteroid which stabilize the polymer. This system appears to be promising for concomitant and contr olled drug delivery aimed at the pharmacological treatment of intraocular p roliferative disorders. (C) 1999 Elsevier Science B.V. All rights reserved.