The Vortex-Slurry Implementation: A Cheap, Easy, and Ultrafast Mechanochemical Tool to Synthesize/Screen Pharmaceutical Salts and Cocrystals

The vortex-slurry implementation is a combination of the best insights taken from multiple solid-state methods using accessible tools to improve the physical scenario, mainly designed for the supramolecular synthesis of new multicomponent pharmaceutical solid forms by coupling mechanochemistry and slurry techniques within a vortex mixer. The proposal of the vortex-slurry implementation is to provide a totally different experimental ambient capable of reaching new 3D thermodynamic states, not allowed in the current commercial mechanochemistry methods (1D mixer mill and 2D planetary mill). The obtained compounds could be easily scaled from milligrams to grams, thus opening the door for the possibility of an industrial scaling approach. The improvements achieved by this new implementation were validated by resynthesizing already reported salts and cocrystals and by presenting a new solid form for the antiviral drug Stavudine (DT4), which is an orally administered second-line drug in HIV treatment. Theoretical studies revealed that this implementation enhances the activation energy of the system due to the ball bearings' helical movements. It is expected that this implementation can spread to the scientific community, allowing manufacturability of new drug candidates and generating improvements in the quality of life of patients.