A comparative study of PLGA microparticle properties loaded with micronized, nanosized or dissolved drug

The objective of this study was to compare properties of poly(lactide-co-glycolide) (PLGA) microparticles loaded with dexamethasone or hydrocortisone in the micronized, nanosized or dissolved state. Dexamethasone and hydrocortisone were nanosized by wet bead milling. The microparticles were prepared by a solvent extraction/evaporation method and were characterized by particle size, encapsulation efficiency, drug solid-state, morphology, in vitro release and dynamic microparticle diameter changes during release. The micronized and nanosized drugs were still in crystalline form after encapsulation into PLGA microparticles with encapsulation efficiencies greater than 85 %. Encapsulating dissolved drugs resulted in lower encapsulation efficiencies (32 to 63 %) and the dissolved drug recrystallized within the PLGA matrix at a higher actual drug loading of 30 %. The order in drug release depended on the physical state of the encapsulated drug and was in the order of dissolved > nanosized > micronized drug. Interestingly, quasi-linear release profiles were obtained with 10 % nanosized dexamethasone in PLGA 502H and 503H microparticles. In conclusion, encapsulating dispersed and, in particular, nanosized drug into PLGA microparticles is a promising tool to increase the encapsulation efficiency, to maintain a stable drug solid-state and to achieve a more continuous release profile.