Biodegradable PLGA microspheres loaded with ganciclovir for intraocular administration. Encapsulation technique, in vitro release profiles, and sterilization process
R. Herrero-vanrell et al., Biodegradable PLGA microspheres loaded with ganciclovir for intraocular administration. Encapsulation technique, in vitro release profiles, and sterilization process, PHARM RES, 17(10), 2000, pp. 1323-1328
Purpose. The purpose of this work was to obtain a sterilized formulation co
nsisting of biodegradable microspheres of poly (DL-lactide-co-glycolide) (P
LGA) for intraocular sustained release of ganciclovir.
Methods. Microspheres were prepared using a dispersion of ganciclovir in fl
uorosilicone oil (FSiO) that was further dispersed in an acetone solution o
f 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 ga
nciclovir from the sterilized and nonsterilized batches were compared using
the similarity factor (f(2)).
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 mum microspheres. T
en mg released ganciclovir in vitro at 1.3 mug/h for the first 21 days, but
decreased to similar to 0.2 mug/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 si
milarly 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.