Artesunate - An investigation into polymorphism

Abstract

Artesunate (ART) is a derivative of artemisinin and is used in the treatment of uncomplicated Plasmodium falciparum (P. falciparum) malaria. Limited and unreliable solid-state and physico-chemical data is currently available for artesunate (ART). Although numerous papers regarding anti-malarial and anti-cancer activities have been published, convincing and consistent information regarding its solidstate forms and physico-chemical properties are lacking. Polymorphs are different crystal forms of the same compound that have different physical and chemical properties. The most popular definition of polymorphism is ‘the ability of any compound or molecule to crystallise as more than one crystalline form’. ART has been reported to occur in different polymorphic forms and there were four entries found in the literature, with reference codes FAHFAV, FAHFAV01, FAHFAV02 and MEXKOP. Three of these entries, FAHFAV, FAHFAV01 and FAHFAV02, are of the same crystalline phase (Form 1) and represent the raw material that is currently commercially found (stereoisomer 10-α-artesunate; orthorhombic with space group P212121). MEXKOP was found to be the ß-isomer of artesunate. A novel solvate of artesunate was prepared and identified during this study, i.e. dichloromethane (DCM) solvate, as well as other possibly new polymorphic forms, which still need to be confirmed through further studies. The powder dissolution results of ART were low, due to the poor water solubility of ART. The DCM desolvate, however, surprisingly showed the best powder dissolution results by increasing the dissolution concentration from 23 μg /ml to 38 μg/ml. To summarise, no new polymorphic forms, nor solvates, nor hydrates, other than Form 1, had been registered in the Cambridge crystallographic data centre (CCDC) for ART to date. Further investigations should be performed to clarify the possibility of the new polymorphic forms, but also to investigate the dissolution results obtained with the DCM desolvate.