Supersaturation-driven self-assembly formation of ceftriaxone sodium spherulites: From amorphous form to spherulites (Open Access)--颗粒学报PARTICUOLOGY

Liang, S., Niu, Y., Hu, X., Xiao, W., Ruan, X., He, G., & Jiang, X. (2024). Supersaturation-driven self-assembly formation of ceftriaxone sodium spherulites: From amorphous form to spherulites. Particuology, 90, 10-19. https://doi.org/10.1016/j.partic.2023.11.018

Supersaturation-driven self-assembly formation of ceftriaxone sodium spherulites: From amorphous form to spherulites (Open Access)

Shankun Liang^a, Yuchao Niu^a, Xueyan Hu^a, Wu Xiao^a, Xuehua Ruan^b, Gaohong He ^{a b *}, Xiaobin Jiang ^a *

a State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials, School of Chemical Engineering, Dalian University of Technology, Dalian, 116024, China
b School of Chemical Engineering at Panjin, Dalian University of Technology, Panjin, 124221, China

10.1016/j.partic.2023.11.018

Volume 90, July 2024, Pages 10-19

Received 14 September 2023, Revised 5 November 2023, Accepted 16 November 2023, Available online 28 November 2023, Version of Record 17 December 2023.

E-mail: hgaohong@dlut.edu.cn; xbjiang@dlut.edu.cn

Highlights

• Supersaturation-driven mechanism of ceftriaxone sodium spherulite formation was revealed.

• Online observation of the amorphous form to spherulites was achieved.

• Adjustable supersaturation region that can improve the morphology of spherulites.

Abstract

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 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. 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.

Graphical abstract

Keywords

Spherulite; Ceftriaxone sodium; Antisolvent crystallization; Supersaturation; Online observation

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