Biodegradable PLGA microspheres loaded with ganciclovir for intraocular administration. Encapsulation technique, in vitro release profiles, and sterilization process.
OBJECTIVE
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.
Herrero-Vanrell
R
R
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA. rociohv@eucmax.sim.ucm.es
Ramirez
L
L
Fernandez-Carballido
A
A
Refojo
M F
MF
D000998:Antiviral Agents / Q000008:administration & dosage* / Q000737:chemistry; D001672:Biocompatible Materials / Q000008:administration & dosage* / Q000737:chemistry; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004333:Drug Administration Routes; D004337:Drug Carriers; D004355:Drug Stability; D005720:Gamma Rays; D015774:Ganciclovir / Q000008:administration & dosage* / Q000737:chemistry; D007700:Kinetics; D019344:Lactic Acid / Q000008:administration & dosage* / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry; D013242:Sterilization / Q000379:methods*; D014822:Vitreous Body
D000998:Antiviral Agents; D001672:Biocompatible Materials; D002214:Capsules; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D015774:Ganciclovir