Direct fractionation of spray-dried polymeric microparticles by inertial impaction

Abstract

The current study describes a convenient method for a direct size classification of spray-dried powders, which is of general interest for diverse applications in drug delivery. Accordingly, the time-consuming “trial-and-error” approach to identify critical formulation and process parameters influencing the final product specifications is replaced by a final fractionation step of the dried particles by inertial impaction.When employing the “original” vibrational spray-dryer (i.e., Nano Spray-Dryer B-90, Büchi) it was evident that both the liquid feed characteristics (e.g., concentration of dissolved solids) and process parameters (e.g., nozzle type and spray-rate) significantly affected the particle size and size distribution of generated sildenafil-loaded poly(lactide-co-glycolide) microparticles (particle size: ~4–~11μm; particle size distribution (span): ~1.3–~2.2). The said formulations showed prolonged in vitro drug release properties with mean dissolution times (MDTs) ranging between ~4 and ~14h. By contrast, replacing the electrostatic particle collector of the vibrational spray-dryer by a Next Generation Impactor enabled a direct size classification of spray-dried microparticles according to their aerodynamic behavior. Formulations collected from the individual impactor stages exhibited a defined particle size (i.e., stages I, II, III and IV with 7.8, 4.5, 3.0 and 2.1μm, respectively) and were significantly narrowly distributed (span: ≤1.2) than the non-fractionated controls. Likewise, fractionated formulations were characterized by a sustained sildenafil in vitro release behavior (MDT: ~1.5–~7h).Overall, regardless of the primary particle size and size distribution of spray-dried powders, desired size characteristics can be achieved by a terminal size classification by inertial impaction. Hence, the described approach provides spray-dried products meeting the specific requirements of the intended application (e.g., prolonged drug delivery to the lungs).