Morphology engineering of a novel poly(L-lactide)/poly(1,5-dioxepan-2-one)microsphere system for controlled drug delivery

Morphology is presented as a powerful tool to control the in vitro degradat ion and drug release characteristics of novel drug delivery microspheres pr epared from homopolymer blends of 1,5-dioxepan-2-one, DXO, and L-lactide, L -LA. Their performance in this respect was compared to analogous P(L-LA-co- DXO) microspheres. Blends formed denser and less porous microspheres with a higher degree of matrix crystallinity than copolymers of corresponding L-L A:DXO composition. The morphology differences of blends and copolymers, fur ther adjustable by means of component ratio, are shown to have a vital impa ct on the in vitro performance. Sustained drug delivery was obtained from b oth copolymers and blends. Molecular weight; loss was retarded and diffusio n-mediated release was inhibited in the latter case, further delaying the r elease process. The effects of storage on the physicochemical properties of these systems were evaluated under desiccated and moist conditions for 5 m onths. Storage-induced physicochemical changes, such as matrix crystallizat ion and molecular weight decrease, were accelerated at higher relative humi dities. P(L-LA-co-DXO) demonstrated higher moisture sensitivity than a PLLA -PDXO blend of corresponding composition. The more crystalline and dense mo rphology of blend microspheres may thus be considered an improvement of the storage stability. (C) 2000 John Wiley & Sons, Inc.