Abstract

Reproducible control of stoichiometry and difficulties in large scale production have been
identified as two of the major challenges to commercial uptake of pharmaceutical co-crystals.
The aim of this research was to extend the application of SFCC to control stoichiometry in
caffeine: maleic acid co-crystals. Both 1:1 and 2:1 caffeine: maleic acid co-crystals were
produced by control of the feedstock composition and process conditions. It was also
observed that formation of 2:1 stoichiometry co-crystals involved formation of a 1:1 cocrystal
which was subsequently transformed to 2:1 co-crystals. The investigation of
stoichiometric transformation revealed that although 1:1 co-crystals could be converted into
2:1 form with addition of excess caffeine, the reverse was not possible in the presence of
excess maleic acid. However, conversion from 2:1 into 1:1 was only achieved by melt
seeding with the phase pure 1:1 co-crystals. This investigation demonstrates that
stoichiometric control can be achieved by SFCC by control of parameters such as extrusion
temperature.