Artemisinin–acetylenedicarboxylic acid cocrystal: screening, structure determination, and physicochemical property characterisation

Abstract

Artemisinin is used to treat multi-drug resistant strains of malaria and is also in the early stages of development as an anti-cancer drug. However, the usage of artemisinin is limited due to its low aqueous solubility. Herein a large scale cocrystal screening of artemisinin was conducted using both computational and experimental approaches, leading to a new 2 : 1 artemisinin and acetylenedicarboxylic acid (ART²–ACA) cocrystal. ART²–ACA crystallises in the P2₁2₁2₁ space group of the orthorhombic system with cell parameters a = 10.5089 Å, b = 24.083 Å, and c = 6.4952 Å. The asymmetric unit of the cocrystal contains two ART molecules and a single ACA molecule, assembled into discrete trimeric units held together by two supramolecular heterosynthons. It was shown that ART²–ACA cocrystals have higher solubility and a faster dissolution rate compared to the parent drug artemisinin.