Crystal Structure of a New 1:1 Acridine-Diclofenac Salt, Obtained with High Yield by a Mechanochemical Approach

Abstract

The liquid-assisted grinding (LAG) approach was exploited to efficiently produce a new salt cocrystal with a minimum expenditure of reagents and energy, with possible application in the pharmaceutical field. LAG was applied to the acridine/diclofenac couple, and a new cocrystal was obtained with a 1:1 ratio of reagents and its structure resolved by X-ray powder diffraction (XRPD). The XRPD analysis confirmed that the yield is higher than 90% and the limited use of solvents and the absence of waste generally makes the synthesis very efficient and with the minimum possible environmental impact. The crystal structure of the title compound was compared to a previously solved 1:2 cocrystal, also with the aid of Hirshfeld’s surface analysis and calculations of the energy framework. The packing of the 1:1 structure is stabilized by a strong H-bond and partial π⋯π-stacking interactions. It differs considerably from that of the previously identified cocrystal, in which two strong hydrogen bonds and a perfect interlocking of the molecules thanks to the the π⋯π stacking induce a much higher stability, as confirmed by energy framework calculations. DSC analysis confirmed its purity and a melting point at 140 °C, which is different from those of the two reactants.

Keywords

• API salt cocrystal
• acridine
• diclofenac
• LAG
• high yield synthesis
• crystal packing