Influence of additives on the release profile of nifedipine from poly(DL-lactide-co-glycolide) microspheres

Abstract

Nifedipine-containing poly(DL-lactide-co-glycolide) (PLGA) microspheres of various sizes and drug contents were prepared by the solvent evaporation 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. Diethylphthalate and Myvacet increased the nifedipine release rate while isopropyl myristate and triacetin had no influence on it. Triacetin seems to be very poorly incorporated into the microspheres. These additives did not modify the degradation rate of the polymer. Differential scanning calorimetry detected a decrease of the glass transition temperature of diethylphthalate-containing microspheres, a small variation with Myvacet, and very little change when triacetin or isopropyl myristate were incorporated. This variation of the glass transition temperature (Tg) tends to imply that nifedipine is released by a diffusion process through the polymer matrix which is enhanced when additives decrease the Tg. Scanning electron microscopy allowed the vizualization of the highly porous structure of microspheres containing the oily substances, and the unchanged smooth surface of diethylphthalate-containing microspheres.

Key Words:

• Microspheres
• nifedipine
• drug release
• poly(lactide-co-glycolide)
• additives