Biodegradable PLGA microspheres loaded with ganciclovir for intraocular administration. Encapsulation technique, in vitro release profiles, and sterilization process.

PURPOSE: The purpose of this work was to obtain a sterilized formulation consisting of biodegradable microspheres of poly (DL-lactide-co-glycolide) (PLGA) for intraocular sustained release of ganciclovir.

METHODS: Microspheres were prepared using a dispersion of ganciclovir in fluorosilicone oil (FSiO) that was further dispersed in an acetone solution of PLGA [50/50 and inherent viscosity 0.41 dl/g], and emulsified in silicone oil with a surfactant. Once prepared, the formulation was exposed with an effective gamma radiation dose of 2.5 megarads. The release rate data of ganciclovir from the sterilized and nonsterilized batches were compared using the similarity factor (f2).

RESULTS: The dispersion of the drug in FSiO contributed to achieving a drug payload of up to 95% of the theoretical in the 300-500 microm microspheres. Ten mg released ganciclovir in vitro at 1.3 microg/h for the first 21 days, but decreased to approximately 0.2 microg/h from day 25 until the end of the release study (42 days). No significant differences in the amounts of encapsulated drug (alpha = 0.05) were observed between the sterilized and nonsterilized microspheres. Furthermore, dissolution profiles of formulations behaved similarly before and after gamma radiation exposure.

CONCLUSIONS: The technique of microsphere preparation described resulted in high ganciclovir loading (95%) and prolonged drug release. The ganciclovir formulation behaved similarly before and after the sterilization process.