Investigation of the factors influencing the release rates of cyclosporin A-loaded micro- and nanoparticles prepared by high-pressure homogenizer

An oil-in-water solvent evaporation method was used to prepare cyclosporin A (CyA)-loaded particles varying in size (nanoparticles, 'small-sized' microparticles, 'large-sized' microparticles), polymer compositions [poly(D,L-lactide-co-glycolic acid) (PLGA) 50/50, PLGA 85/15, poly(D,L-lactic acid) (PLA)] and additive fatty acid ester (ethyl myristate; EM). The particles were characterized for drug loading and entrapment efficiency by high-performance liquid chromatography, particle size by dynamic light scattering and surface morphology by scanning electron microscopy (SEM). In vitro release kinetics were studied using a modified dialysis method. The results showed drug loadings ranging from 6.48 to 9.01% with high encapsulation efficiency (71.2-98.9%). SEM studies showed discrete and spherical particles with smooth surfaces, whereas rather gross surface defects resulted from the incorporation of EM as an additive. The release profiles of various formulations approximated zero-order release kinetics in the first 3 weeks with a negligible initial burst. In general, the smaller the particle size and the higher the glycolic acid content in the copolymer, the faster the release of CyA. The effect of EM on the release profile appeared to be rather complex since an increased release rate was observed from EM containing PLGA 50/50 particles, whereas the incorporation of EM into the PLGA 85/15 and PLA particles led to a decreased release rate. Further investigation needs to be performed to elucidate the reason why EM influences the CyA release differently depending on the particle size and polymer type. (C) 2002 Elsevier Science B.V. All rights reserved.