Drug particles with spherical morphology possess amazing advantages in terms of particle flowability, mechanical properties, drug solubility, and bioavailability. 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 was higher than 2.62, the crystallization system tended to appear amorphous form; when was between 2.57 and 2.62, the amorphous form transformed into clustered spherulites; when was less than 2.57, the surface of spherulites will be covered with flaky crystal, which transformed into urchin-like type. With the understanding of the spherical growth mechanism, the ceftriaxone sodium spherulites prepared in this research with modified supersaturation control had a low residue of antisolvent acetone, and the flowability was significantly improved.

中文翻译：

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过饱和驱动的头孢曲松钠球晶的自组装形成：从无定形到球晶

球形药物颗粒在颗粒流动性、机械性能、药物溶解度和生物利用度方面具有惊人的优势。药物球晶的生长机理对于球晶的制备和调控具有重要意义。在此，通过将头孢曲松钠溶液滴加到丙酮中的反溶剂结晶方法制备了头孢曲松钠球晶。结合电子显微镜技术在线观察整个结晶过程，揭示了从非晶态到球晶的球形生长过程。随着结晶体系过饱和度的调节，头孢曲松钠晶体由无定形转变为球晶。以丙酮为反溶剂的反溶剂结晶过程中，当理论过饱和度高于2.62时，结晶体系趋于无定形；当在2.57和2.62之间时，无定形形态转变为簇状球晶；当小于2.57时，球晶表面被片状晶体覆盖，转变为海胆状晶体。随着对球形生长机制的了解，本研究采用改良过饱和度控制制备的头孢曲松钠球晶，反溶剂丙酮残留量低，流动性显着改善。