EVALUATION OF 90 10 POLY(D,L-LACTIDE-CO-GLYCOLIDE) MICROSPHERES CONTAINING NORETHISTERONE - DRUG-RELEASE AND BIODEGRADATION/

Poly(D,L-lactide-co-glycolide) (PLG, 90:10) microspheres containing 20 % norethisterone (NET) were prepared by solvent evaporation method. Mi crospheres in the size ranges of 65 to 100 mum were sterilized by irra diation and used for further study. In vitro release showed fairly con stant release of NET from the above microspheres over more than 90 day s. However, in vivo drug release determined by residual NET analysis a fter i.m. injection in rats indicated a faster release rate. About 95% of NET was released in a period of 45 days. At the dose of 80 mg of m icrospheres, vaginal estrus cycles were inhibited for 45 days compared to 27 days for the same dose of NET crystals in rats. Biodegradation of the microspheres was tested by direct measurement of molecular weig ht losses and SEM observation of morphological changes of the microsph eres, which showed continuous erosion in the internal matrix of micros pheres with the decrease of molecular weight of PLG until total collap se of microspheres, and biodegradation was faster in rats than in huma n serum at 37-degrees-C in vitro. Total degradation of 90:10 PLG micro spheres was less than 7 months in rats and more than 9 months in vitro .