Optimization of budesonide-loaded large-porous microparticles for inhalation using quality by design approach

Abstract The aim of this study was to apply a quality by design (QbD) approach for the development of budesonide (BUD)-loaded large porous microparticles (LPPs) for inhalation purpose. An Ishikawa diagram was used to analyze all relevant factors and potential parameters with high risks were identified. Single factor studies were carried out to investigate the influence of drug loading, poly(lactide- co -glycolide) type and concentration on the properties of the LPPs. Next, a central composite design/response surface method was used to study the potential influence of high risks parameters, including O/W phase ratio, poly(vinyl pyrrolidone) (PVP) and poly(vinyl alcohol) (PVA) concentration, with respect to the geometric particle size, fine particle fraction (FPF) and drug encapsulation efficiency (EE). When the O/W phase ratio and PVP amount in the organic phase were decreased, smaller particles with a higher EE were obtained. Furthermore, the BUD-loaded LPPs were less porous upon an elevation of PVA concentration in the aqueous phase. After having identified these relevant parameters/conditions optimized BUD-loaded LPPs could be prepared with an EE of >60% and an aerodynamic particle size of ∼6 μm (FPF>21%). Overall, QbD approach enabled the fabrication of optimized BUD-loaded LPP formulations for inhalation therapy.