Effect of ethanol as a processing co-solvent on the PLGA microsphere characteristics

Area of Science:

• Biomaterials Science
• Pharmaceutical Technology
• Drug Delivery Systems

Background:

• Poly(lactide-co-glycolide) (PLGA) microspheres are widely used for controlled drug delivery.
• Dexamethasone is a potent corticosteroid with various therapeutic applications.
• Optimizing microsphere formulation is crucial for effective drug delivery.

Purpose of the Study:

• To evaluate the impact of ethanol as an organic co-solvent on dexamethasone-loaded PLGA microspheres.
• To determine the maximum permissible ethanol concentration for preparing radio-labeled dexamethasone PLGA microspheres without compromising performance.
• To understand how varying ethanol concentrations influence microsphere physicochemical properties and in vitro release.

Main Methods:

• PLGA microspheres loaded with dexamethasone were prepared using the emulsion-solvent evaporation/extraction method.
• Different concentrations of ethanol (0-43.75% v/v) were employed as an organic co-solvent.
• Physicochemical properties (particle size, drug loading, morphology) and in vitro release profiles were analyzed.

Main Results:

• Particle size significantly decreased at 12.5% ethanol, and drug loading decreased at 25% ethanol.
• Drug crystals formed on microsphere surfaces at ethanol concentrations of 18.75% and higher.
• Increased burst release was observed for formulations with surface drug crystals.
• Interfacial tension, drug solubility, and polymer viscosity influenced microsphere characteristics.

Conclusions:

• Ethanol concentration critically affects dexamethasone PLGA microsphere characteristics and drug release.
• Up to 12.5% (v/v) ethanol can be incorporated into the organic phase for radio-labeled dexamethasone microsphere preparation without significant adverse effects.
• Formulations with higher ethanol concentrations exhibit altered properties and release kinetics due to surface drug crystallization.