Microspheres prepared with PLGA blends for delivery of dexamethasone for implantable medical devices.
OBJECTIVE
To develop and characterize microspheres using poly (lactic-co-glycolic acid) (PLGA) blends (PLGA5050 (25 KD) and PLGA6535 (70 KD)) for dexamethasone delivery to prevent foreign body response to implantable biosensors.


METHODS
A single emulsion based oil/water solvent evaporation/extraction method was used to prepare microspheres.


RESULTS
All the microspheres prepared exhibited the typical triphasic release profile, but with different initial burst release, lag phase and zero order release rates. The burst release was reduced when the two PLGA were mixed at a molecular level, whereas increase in burst release was observed when phase separation occurred. Microspheres prepared using PLGA blends had significantly shorter lag phase. The activation energy (Ea) of dexamethasone release from microspheres was similar to the Ea value of PLGA degradation. The release kinetics were significantly enhanced under accelerated conditions (45 and 53°C) without altering the release mechanism of the post-burst phase. A rank order correlation between accelerated and "real-time" release kinetics was observed.


CONCLUSIONS
Polymer blends of PLGA can produce microspheres with reduced lag time. The accelerated release testing conditions investigated can discriminate the formulations and predict "real-time" release. Such accelerated release testing can be used as a rapid screening method to facilitate formulation development.
Department of Pharmaceutical Sciences, University of Connecticut, 69 N Eagleville Rd U3092, Storrs, Connecticut, 06269, USA.
Yan
Y
Wang
Bing
B
Gu
Diane J
DJ
Burgess
D002626:Chemistry, Pharmaceutical / Q000379:methods; D003907:Dexamethasone / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D004655:Emulsions / Q000737:chemistry; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D009821:Oils / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D019736:Prostheses and Implants; D012997:Solvents / Q000737:chemistry; D014867:Water / Q000737:chemistry
D004655:Emulsions; D009821:Oils; D011108:Polymers; D012997:Solvents; D014867:Water; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone