Lorena Pasero, Adamo Sulpizi, Tomaso Guidi, Roberto Pisano
Abstract
In this study, microparticles carrying salbutamol sulphate were produced by pneumatic spray freeze-drying. The optimal particle size was assessed through a model, associated with a design of experiments. Growing solid concentrations and flow rate led to decreasing geometric diameters, while an opposite effect was associated with the feed flow rate. The aerodynamic diameter, instead, increased at increasing solid concentrations. Moreover, the role of crystallinity in determining the microparticles’ flowability was evaluated upon the incorporation of L-leucine. The addition of the amino acid induced the formation of two morphologies with different degrees of crystallinity. The absence of recrystallization significantly improved the aerosolization properties of the microparticles up to a maximum fine particle fraction (48 %) and a minimum mass median aerodynamic diameter (2 μm) at 10 % (w/w db) L-leucine. This result disclosed the influence of polymorphism on the microparticles’ cohesiveness, proving the dependency of the microparticles’ aerodynamics on L-leucine and mannitol crystallinity.
Keywords:
Spray freeze-drying, Inhalable microparticles, Inter-particle cohesiveness, Leucine, Polymorphism, Aerosolization