Processing of spherical crystalline particles via a novel solution atomization and crystallization by sonication (SAXS) technique

Purpose. The objective was to develop a single-step pharmaceutical particle engineering technique able to produce particles within a well-defined particle size range while controlling macroscopic spherical morphology and mesoscopic surface topography. Methods. Paracetamol ( acetaminophen) aerosol droplets were generated by spraying a solution via either an electrohydrodynamic atomizer ( EHDA) or an air pressure atomizer. The highly supersaturated droplets were collected in a suitable nonsolvent of the drug and crystallized by ultrasonication. Suspended particles were filtered, and their physicochemical properties characterized. Results. The SAXS processed particles showed a relatively homogeneous particle size distribution between 1 and 5 mum. Particles were nominally crystalline in structure. The chemical structure of the active ingredient did not apparently alter during processing. Controlling the solute concentration of the air pressure atomized solution provided a means of controlling the degree of sphericity and particle-size characteristics. In comparison to micronized paracetamol particles, SAXS-produced particulates were generally more uniform in shape with increased nanometer surface roughness. Conclusions. The SAXS process provides a novel means of producing crystalline particles in a well-defined particle size range. Furthermore, the method offers a range of opportunities in controlling physical properties including surface topography and particle shape.