Primary crystal growth during spherical agglomeration in liquid: designing an ideal dry powder inhalation system

Spherical agglomerates of steroid KSR-592, consisting of fine primary drug crystals suitable for dry powder inhalation (DPI), were prepared by the spherical agglomeration method in liquid with a bridging liquid. It was found that the particle size of primary crystals increased until the dispersing medium was saturated with the bridging liquid introduced to the system, whereas the spherical agglomeration of primary crystals continued even after the saturation. The growth rates of primary crystals and agglomerates increased with an increase in the temperature and/or a reduction in the agitation speed of the system. The growth of primary crystals in the spherical agglomerates was explained by a crystallization and fusion mechanism proposed by us. The primary crystals were mechanically stronger than their agglomerates so that the agglomerates were disintegrated easily into the primary crystals, which retained their original size, under the shear force generated on being mixed with carrier particles for DPI.