Supersaturation-driven self-assembly formation of ceftriaxone sodium spherulites: From amorphous form to spherulites

The growth mechanism of drug spherulite is of great importance for the preparation and regulation of spherulites. Herein, ceftriaxone sodium spherulites were fabricated by the antisolvent crystallization method using dropwise addition of ceftriaxone sodium solution to acetone.

Online observation of the whole crystallization process combined with electron microscopy technique revealed the spherical growth process from amorphous form to spherulites. As the supersaturation of the crystallization system was adjusted, the ceftriaxone sodium crystals transformed from amorphous form to spherulites. In the process of antisolvent crystallization with acetone as antisolvent, when the theoretical supersaturation degree S was higher than 2.62, the crystallization system tended to appear amorphous form; when S was between 2.57 and 2.62, the amorphous form transformed into clustered spherulites; when S was less than 2.57, the surface of spherulites will be covered with flaky crystal, which transformed into urchin-like type.