Parameters determining the agglomeration behaviour and the micromeritic properties of spherically agglomerated crystals prepared by the spherical crystallization technique with miscible solvent systems

Abstract The parameters determining the agglomeration behaviour and micromeritic properties of spherically agglomerated crystals of acebutolol hydrochloride prepared by the spherical crystallization technique with a two- or three-miscible-solvent system (i.e., bridging liquid, good solvent, poor solvent) were investigated. With decreasing amount of water (= bridging liquid) in the three-solvent system, the median diameter of agglomerated crystals increased, having a wider size distribution. When the composition of the system approached that of phase separation (= saturation with water), smaller sized agglomerates with a narrower size distribution were produced. The median diameter of agglomerates decreased with increasing content of ethanol (= good solvent) in the formulation. Spherically agglomerated crystals were produced evenly with the two-solvent system, i.e., water and isopropyl acetate (= poor solvent), in which the water played both the roles of bridging liquid and good solvent. The median diameter of agglomerates decreased with increasing agitation speed of the system.