Direct fractionation of spray-dried polymeric microparticles by inertial impaction

•Vibrational spray-drying was influenced by feed solution and process parameters.•Obtained powder formulations were of rather “heterogeneous” nature.•Powders were classified by replacing the standard particle collector by an impactor.•Fractionated formulations exhibited defined particle size characteristics.•This approach is useful for a rapid preparation of tailored spray-dried formulations.

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–~ 11 μm; 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 ~ 14 h. 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 2.1 μm, 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–~ 7 h).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).

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