Micromeritic characteristics and agglomeration mechanisms in the spherical crystallization of bucillamine by the spherical agglomeration and the emulsion solvent diffusion methods

Abstract

The physical properties of bucillamine were modified by the application of two spherical crystallization techniques — the spherical agglomeration and the emulsion solvent diffusion methods. The mechanisms of spherical agglomeration and crystallization were investigated. In the spherical agglomeration method, the microcrystalline drug precipitates were aggregated via liquid bridges of dichloromethane liberated from the crystallization solvent system. The growth rates were mainly determined by the amount of dichloromethane formulated. In the emulsion solvent diffusion method, the drug was precipitated within finely dispersed ethanol drops and these quasi-emulsion droplets were transformed into rigid spherical agglomerates. The mechanism determining the structure of the resultant agglomerates was clarified by measuring their mechanical strength. The crystal binding points within agglomerates produced by the spherical agglomeration method were distributed uniformly through the entire cross-section, whereas in the agglomerates prepared by the emulsion solvent diffusion method, they were localized in the agglomerate surface crust.