ARA-C RELEASE FROM POLY(ACRYLAMIDE-CO-MONOMETHYL ITACONATE) HYDROGELS- IN-VITRO AND IN-VIVO STUDIES

Cytarabine (ara-C) release from copolymeric poly(acrylamide-co-monomet hyl itaconate) (A/MMI) hydrogels was studied. Three different composit ions of copolymers were studied, 90A/10MMI, 75A/25MMI and 60A/40MMI. T he drug was trapped in gels by placing it in the polymerization feed m ixture and discs loaded with 5-50 mg of ara-C were obtained. Drug rele ase kinetics were examined as a function of temperature and drug load. The diffusion kinetics followed Fick's second law. The diffusion coef ficients for the release of ara-C were between 5.7x10(-11) and 9.6x10( -11) m(2)s(-1). To determine the applicability of these copolymers, 75 A/25MMI gel was subcutaneously implanted in rats and the drug plasma c oncentration was determined by HPLC. The ara-C plasma concentration is constant (range 11.2 +/- 1.1 mu g/ml-12.8 +/- mu g/ml) during the fir st stages (2-8 h) and no drug was detected after 31 h. (C) 1998 Elsevi er Science Ltd. All rights reserved.