Abstract
This thesis investigates the mechanisms governing droplet-microfluidic fabrication of poly (lactic-co-glycolic-acid) (PLGA) microparticles loaded with Levosimendan (LS) and their impact on drug encapsulation and release, while establishing predictive frameworks to guide process optimisation. By tuning key operating parameters, precise control over particle size (2-25 μm), morphology and narrow size distributions (PDI < 0.5) was achieved across two scales. PLGA microparticles as small as 2 μm were produced within the dripping regime without post-processing. Experimental studies combined with computational fluid dynamics (CFD) simulations demonstrated that internal droplet hydrodynamics strongly influence solvent diffusion, polymer precipitation and particle formation. This analysis enabled linking between the intensity of vortices within the droplet and particle size, providing a mechanistic understanding of how microfluidic conditions govern particle formation. Predictive correlations for droplet and particle size showed average deviations below 10 % while CFD simulations showed good agreement with experimental droplet formation. LS-loaded microparticles achieved encapsulation efficiencies of 40-64 % and drug loading up to 28 %, with sustained drug release over four days and tunable burst release behaviour. The results demonstrate that droplet hydrodynamics and mass transfer govern particle formation and therapeutic performance, providing a predictive framework for controlled microfluidic synthesis of drug delivery systems.