Evidence for flocculation-controlled microcrystallisation of salmeterol xinafoate

Abstract

The therapeutic management of pulmonary disease depends upon the efficient delivery of aerosolized drug particles with an aerodynamic diameter of 2.5–6 mm (Pritchard 2001). Particles for such aerosols are routinely produced by jet milling, which can lead to the generation of amorphous regions on the surface or polymorphic conversion. An alternative strategy to directly crystallize the drug and limit subsequent particle growth, would provide the opportunity to avoid potential crystal modification during processing. Precipitation at high supersaturation produces primary particles in the low micron sizerange, but secondary growth frequently follows the aggregation and agglomeration of these primary particles (Yu et al 2005). The aim of this study was to investigate the control of crystal growth of salmeterol xinafoate (SX) during crystallization from an aqueous phase