Simultaneous improvement of physical stability, dissolution, bioavailability, and antithrombus efficacy of Aspirin and Ligustrazine through cocrystallization

Kairu Wang; Yanshuang Hao; Chenguang Wang; Xinghua Zhao; Xin He; Changquan Calvin Sun

doi:10.1016/j.ijpharm.2022.121541

Simultaneous improvement of physical stability, dissolution, bioavailability, and antithrombus efficacy of Aspirin and Ligustrazine through cocrystallization

Int J Pharm. 2022 Mar 25:616:121541. doi: 10.1016/j.ijpharm.2022.121541. Epub 2022 Feb 3.

Authors

Kairu Wang¹, Yanshuang Hao², Chenguang Wang³, Xinghua Zhao¹, Xin He⁴, Changquan Calvin Sun⁵

Affiliations

¹ College of Veterinary Medicine, Hebei Agricultural University, Baoding, Hebei 071000, China.
² College of Animal Science and Technology, Hebei Agricultural University, Baoding, Hebei 071000, China.
³ Pharmaceutical Materials Science and Engineering Laboratory, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA.
⁴ College of Veterinary Medicine, Hebei Agricultural University, Baoding, Hebei 071000, China. Electronic address: dyhexin@hebau.edu.cn.
⁵ Pharmaceutical Materials Science and Engineering Laboratory, Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: sunx0053@umn.edu.

PMID: 35124115
DOI: 10.1016/j.ijpharm.2022.121541

Abstract

A novel 1:1 cocrystal between two cardiovascular drugs, aspirin (ASA) and ligustrazine (tetramethylpyrazine, TMP) has been synthesized and characterized. The structure of this drug-drug cocrystal, ASA-TMP, was determined using single crystal X-ray crystallography. The ASA-TMP cocrystal exhibits a significantly reduced sublimation tendency than TMP. Importantly, cocrystallization simultaneously improves bioavailability of both parent drugs. This suggests the possibility of developing a more effective antithrombosis drug therapy given the synergistic pharmacological effects of the two parent drugs.

Keywords: Antithrombosis; Aspirin; Bioavailability; Cocrystal; Ligustrazine.

MeSH terms

Aspirin*
Biological Availability
Crystallization
Pyrazines
Solubility

Substances

Pyrazines
Aspirin
tetramethylpyrazine