Design and mechanism of agglomeration of aspirin crystals in pure solvents--颗粒学报PARTICUOLOGY

Jia, L., Wu, D., Cui, P., Zhou, L., & Yin, Q. (2023). Design and mechanism of agglomeration of aspirin crystals in pure solvents. Particuology, 82, 146-156. https://doi.org/10.1016/j.partic.2023.01.018

Design and mechanism of agglomeration of aspirin crystals in pure solvents

Lihong Jia ^a, Degui Wu ^a, Pingping Cui ^a, Ling Zhou ^a *, Qiuxiang Yin ^{a b c *}

a School of Chemical Engineering and Technology, State Key Laboratory of Chemical Engineering, Tianjin University, Tianjin, 300072, China
b Haihe Laboratory of Sustainable Chemical Transformations, Tianjin, 300192, China
c Tianjin Key Laboratory of Modern Drug Delivery and High Efficiency, Tianjin, 300072, China

10.1016/j.partic.2023.01.018

Volume 82, November 2023, Pages 146-156

Received 28 September 2022, Revised 16 January 2023, Accepted 31 January 2023, Available online 17 February 2023, Version of Record 21 February 2023.

E-mail: zhouling@tju.edu.cn, qxyin@tju.edu.cn

Highlights

• Obtain agglomerates of platy aspirin by cooling crystallization in pure solvents.

• Determine suitable solvents and the maximum stirring rate for agglomeration.

• Elucidate a feasible mechanism for the agglomeration process of platy crystals.

• Study the effect of stirring rate, cooling rate, and supersaturation on agglomeration.

Abstract

Agglomeration with improved flowability for platy crystals is desirable in pharmaceutical downstream processing. The formation of agglomerates in pure solvents without the aid of bridging liquids is a convenient and low-cost method compared with complex spherical crystallization. In this work, the adhesion free energies between aspirin crystals in six solvents were calculated using Lifshitz-van der Waals acid-base theory to screen suitable solvents for agglomeration. The maximum stirring rate for agglomeration was determined by adhesion forces and dispersion forces. Then the agglomerates of plate-shaped aspirin were successfully prepared in acetone, methanol, ethanol, 2-propanol, and ethylene glycol without additives by simple cooling crystallization. The interactions between solvent and crystal surfaces were also used to explain the outcomes. A feasible mechanism for the agglomeration process of platy crystals was elucidated, involving the adhesion of dominant crystal facets at the beginning. The effect of stirring rate, cooling rate, and initial supersaturation on agglomeration degree and particle size of aspirin agglomerates were studied. The obtained aspirin agglomerates under the optimal conditions exhibited a uniform particle size distribution, a high agglomeration degree, and superior flowability.

Graphical abstract

Keywords

Agglomeration; Platy crystal; Aspirin; Adhesion force

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