INFLUENCE OF ADDITIVES ON THE RELEASE PROFILE OF NIFEDIPINE FROM POLY(DL-LACTIDE-CO-GLYCOLIDE) MICROSPHERES

Nifedipine-containing poly(DL-lactide-co-glycolide) (PLGA) microsphere s of Various sizes and drug contents were prepared by the solvent evap oration method. The in vitro release profiles of nifedipine from PLGA microspheres and the degradation pattern of the polymer were evaluated . Four additives were incorporated in the microspheres: two non-fatty plasticizers: diethylphthalate and triacetin, and two fatty substances : isopropyl myristate and Myvacet(R) Diethylphthalate and Myvacet incr eased the nifedipine release rate while isopropyl myristate and triace tin had no influence on it. Triacetin seems to be very poorly incorpor ated into the microspheres. These additives did not modify the degrada tion rate of the polymer. Differential scanning calorimetry detected a decrease of the glass transition temperature of diethylphthalate-cont aining microspheres, a small variation with Myvacet(R), and very littl e change when triacetin or isopropyl myristate were incorporated. This variation of the glass transition temperature (Tg) tends to imply tha t nifedipine is released by a diffusion process through the polymer ma trix which is enhanced when additives decrease the Tg. Scanning electr on microscopy allowed the vizualization of the highly porous structure of microspheres containing the oily substances, and the unchanged smo oth surface of diethylphthalate-containing microspheres.