FORMULATION AND RELEASE KINETICS OF CEPHALEXIN MONOHYDRATE FROM BIODEGRADABLE POLYMERIC MICROSPHERES

Sustained release cephalexin microspheres have been formulated with po ly(L-lactic acid) for intraperitoneal administration. Microspheres wer e prepared with spray-dried cephalexin by phase separation in organic solvent containing a fixed concentration of polymer, then sieve-sized. Batch-to-batch reproducibility of microsphere size distribution and e ncapsulation efficiency (>95%) were demonstrated. The quality of the m icrospheres was dependent on the rate of stirring during preparation a nd was highest as 400 rpm. Scanning electron micrographs revealed appr oximately spherical shapes and porous surfaces. The release of cephale xin followed second order dissolution model kinetics for multiparticul ate systems. The apparent second order rate constant, k(2), was lowest for the highest sieve-size fraction (250-425 mu m) and varied with dr ug loading reaching a minimum at 33% w/w. A lower molecular weight PLA of 50 000 produced a faster release of cephalexin from microspheres. Cephalexin was released from microspheres for at least 4 h compared to only 10 min for complete dissolution of an equivalent weight of cepha lexin powder, indicating sustained release which may be appropriate in treating localized infections.