Abstract
Sustained-release approaches are emerging for the delivery of drugs from polymer encapsulation. However, the most persistent problem that remains is the initial burst release of the drug, which can exceed the toxic limits. Dexamethasone, a hydrophobic drug, was encapsulated in poly(lactide-co-glycolide) (PLGA) microparticles using the solvent evaporation method. The drug release profile of these microparticles was studied and the initial burst was reduced by crosslinking of the microparticle surface using ethylene glycol dimethacrylate and tri(ethylene glycol) dimethacrylate. Due to surface crosslinking, an additional diffusional resistance was created, which prevented easy dissolution of the drug into the release medium and brought about a substantial reduction in the initial burst release. Moreover, the time required for reaching a stationary-state release was also observed to be delayed, prolonging the sustained drug delivery. This concept was further tested with a hydrophilic drug, the sodium salt of dexamethasone phosphate, encapsulated in PLGA polymer microparticles and was observed to reduce the burst release as well. For synthesizing the polymer microparticles containing dexamethasone, an o/w microemulsion and solvent evaporation technique was used; whereas, for those containing dexamethasone phosphate, w/o/o/o phase separation/coacervation technique was used. The surface crosslinking was performed by ultraviolet radiation.
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