Mupirocin calcium-loaded poly(meth)acrylic-based microparticles were prepared using spray drying technique. The influence of drug:polymer ratio (5:1, 2:1, 1:1, 1:2, 1:5, w/w), inlet temperature (70 - 110°C), feed concentration (1%-5%, w/w), feed solvent and physical forms of the polymer on drug encapsulation, yield, in vitro drug release, morphology, particle size and solid state properties of the microparticles were investigated. Morphology and particle size were determined using low-angle laser light scattering and scanning electron microscopy. Profound solid state characterization of the microparticles was conducted using X-ray powder analysis (XRPD), thermogravimetric analyses (TGA), modulated differential scanning calorimetry (MDSC), Fourier transformed infrared spectroscopy (FTIR) and Fourier transformed Raman spectroscopy (FT Raman). Mathematical modelling (monoexponential and biexponential equations) was applied to characterize drug release kinetics. In addition, a time-kill assay was performed using S. aureus (ATCC 29213) and clinically isolated methicillin-resistant S. aureus (MRSA) strains at two concentrations in order to evaluate the antimicrobial activity of microsystems. The best control over mupirocin release was achieved for 2:1, w/w drug:polymer ratio and found to be strongly process-dependant. The increased feed concentration (>4%) resulted in higher burst release due to looser matrix formation, whereas increased inlet temperature (≥100°C) reduced burst release since formation of polymer matrices was enhanced by higher molecular mobility and lower solvent residues. The superior control of drug release from microparticles was achieved with a 2:1, w/w drug:polymer ratio using solvents in the following order: methanol ≈ methanol:ethanol (50:50, w/w) > isopropanol:acetone (40:60, w/w). The physical aging of the solid dispersion after ten months of storage had negligible impact on the microparticle performance. Moreover, a time-kill assay performed on S. aureus (ATCC 29213) and methicillinresistant S. aureus (MRSA) confirmed a prolonged release and preservation of antimicrobial activity of encapsulated drug. In general, variations of initial saturation of drug/polymer, inlet temperature or solvent used, were recognised as efficient tools to modulate the formation of proper polymer matrices. Drug loading solely is not a sufficient and reliable predictor of drug release pattern and should be evaluated in conjunction with corresponding processing parameters. Complete encapsulation of drug was achieved in all microparticles prepared from feed solution. Solid dispersions are frequently generated in the spray drying process. The obtained solid dispersions are either solid solutions or inhomogeneous solid dispersions containing amorphous drug clusters depending on the drug:polymer ratio. Controlled drug release was achieved from amorphous solid solutions only if well-formed (denser) polymer matrix was generated later in drying process (which could be tailored via appropriate spray drying processing).