Exploring the Potential of Electrospray Technology in Cocrystal Synthesis

Ind. Eng. Chem. Res., Article ASAP

DOI: 10.1021/acs.iecr.6b01938

The objective of the current paper was to screen potential of electrospray technique for synthesis of cocrystals from a most challenging caffeine (CA)/maleic acid (MA) pair. Additionally, the influence of solvent properties on the formation of a cocrystal form was also investigated. CA and MA were dissolved in a sufficient amount of methanol, ethyl acetate, acetone, and water separately so as to obtain 1:1 and 2:1 equimolar ratios. The prepared solutions were electrosprayed at a voltage of 20 kV. The cocrystals formed from these solvents with diverse physicochemical properties were analyzed by X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy. Methanol, acetone, ethyl acetate, and water have H-bond acceptor/donor (HBA/HBD) values of ≥0.5, 0, 0, and ≥0.5, respectively. CA/MA in 1:1 form I and II were formed predominantly from methanol, ethyl acetate, and acetone regardless of the starting composition. It was observed that, in spite of having zero HBA/HBD value, ethyl acetate and acetone showed formation of 1:1 form I and II CA/MA cocrystals. Surprisingly, 2:1 cocrystals of CA/MA were formed from water. Thus, in the current work the potential of an electrospray technique for continuous manufacturing of cocrystals has been reported for the first time.