Microfluidic Production of Dexamethasone-Loaded PLGA Microparticles: Dynamic Solvent Extraction Improves Process Robustness During the Droplet-to-Particle Transition.

Background/

Objectives

Poly(lactic-co-glycolic acid) (PLGA) microparticles are used for sustained drug delivery, yet their final quality depends on both initial droplet formation and the subsequent solvent-extraction-driven droplet-to-particle transition. Microfluidics provides excellent control over precursor droplets, but this control may be partially lost during particle formation. We previously developed dynamic solvent extraction (DSE), in which the droplet-to-particle transition occurs progressively during continuous transport through an extended microfluidic channel. Here, we investigated whether this control improves quality attributes and release of drug-loaded PLGA microparticles.

Methods

Dexamethasone (DEX)-loaded PLGA microparticles were produced using DSE or static solvent extraction (SSE), in which microfluidic droplets were transferred to an external aqueous medium for particle formation. Three PLGA concentrations (2.5, 5, and 10% (w/v)) were investigated, with processing conditions selected to obtain comparable final particle sizes and reduce size as a confounding variable.

Results

DSE significantly reduced particle-size coefficient of variation compared with SSE, indicating better preservation of size uniformity. Drug loading and encapsulation efficiency were governed mainly by PLGA concentration, with no significant effect of extraction strategy. Morphological effects were formulation-dependent, with the most pronounced defects in 5% (w/v) SSE particles. All formulations provided sustained DEX release over 70 days. Although the overall effect of extraction strategy on 24 h burst release was not statistically significant, DSE consistently produced numerically lower burst release, with the largest and most variable burst observed for the morphologically heterogeneous 5% (w/v) SSE formulation.

Conclusions

These findings extend DSE to drug-loaded sustained-release microparticles and identify the solvent-extraction environment as an important determinant of final particle quality.