Effect of ganciclovir on the hydrolytic degradation of poly(lactide-co-glycolide) microspheres

Ganciclovir (GCV)-loaded poly(lactide-co-glycolide) (PLGA) microspheres, 125 +/- 11 mum in diameter, are produced using the emulsification/solvent evaporation technique. The release rate of the drug is studied for 20 weeks in a phosphate-buffered solution of pH 7 at 37 degrees C. The release of the drug shows a triphasic release pattern, i.e., an initial burst, a diffusive phase, and a second burst. The initial burst occurs within the first 2 days of immersion. After the burst, the release is by diffusion for up to 13 weeks, followed by another burst release, which signals the onset of bulk degradation of the PLGA polymer. The presence of GCV molecules decreases the hydrolytic rate of PLGA degradation. Gel permeation chromatography (GPC), differential scanning calorimetry (DSC), field emission scanning electron microscopy (FESEM), and ultraviolet (UV) spectroscopy are used to assess the hydrolytic degradation and drug release rate of the microspheres.