Hollow and Solid Spherical Azithromycin Particles Prepared by Different Spherical Crystallization Technologies for Direct Tableting

Many drugs have a propensity for agglomeration, resulting in poor flowability. Spherical crystallization can be used to improve product properties including flowability and particle size. In this work, two methods were developed and utilized to successfully make two kinds of azithromycin spherical particles, namely solid and hollow spheres. The resultant product exhibited regular spherical shape, large particle size, narrow particle size distribution and excellent flowability. The formation mechanism of these different spherical crystals was investigated with the help of a particle vision microscope (PVM). The immersion mechanism and the counter diffusion mechanism were proposed as the formation mechanisms for solid and hollow spheres, respectively. The effects of crystallization parameters on the spherical crystallization processes were investigated systematically. Furthermore, the tablet properties were evaluated to verify that the spherical particles obtained in this work can be directly used for tableting, thus avoiding granulation processes and reducing cost.