IN-VITRO DRUG-RELEASE FROM SELF-CATALYZED POLY(ORTHO ESTER) - CASE-STUDY OF 5-FLUOROURACIL

Self-catalyzed poly(ortho esters) are a new variation of linear poly(o rtho esters) prepared by the addition of diols to the diketene acetal 3,9-diethylidene-2,4, 8,10-tetraoxaspiro[5,5]undecane where dimer segm ents of lactic acid or glycolic acid are built into the polymer backbo ne. By varying the concentration of these segments, polymer erosion ra te can be controlled. The present investigation describes the in vitro drug release characteristics from these new polymers. Because poly(or tho esters) have potential applications for the delivery of antifibrob lastic agents for example after glaucoma-filtering surgery, the in vit ro release studies were evaluated using 5-fluorouracil as the active c ompound. It was shown that a mole ratio of 90/10 or 80/20 diol/diol-la ctate incorporated into the polymer lead to a release of 5-fluorouraci l by an erosion process. Smaller amounts of diol-lactate lead to a con comitant drug release by diffusion and erosion. It was also shown that the release rate depends on the alkyl chain length of the diol in the polymer backbone but it does not depend on the drug loading. (C) 1998 Elsevier Science B.V. All rights reserved.