Evaluation of two and three fluid nozzle spray drying to prepare co-crystals of salicylic acid and caffeine with improved physicochemical properties

Formation of co-crystals using spray drying remains a challenging task due to the rapid nature of the process and the possible impact of solvents on the formation of the co-crystals. The purpose of this work was to generate cocrystals via two-fluid and three-fluid nozzle spray drying using the model system of salicylic acid and caffeine (SAL-CAF). The prepared co-crystal showed a strong tendency to form through spray drying, from a variety of feedstock compositions and through both two-fluid and three-fluid drying methods. Powder X-ray diffraction, Fourier - Transform infrared spectroscopy and differential scanning calorimetry were used to characterise the spray dried powders through comparison to the reported crystal structure and SAL-CAF formed through milling. All spray dried powders showed good agreement to the reported crystal structure but with an additional phase present, determined as the beta-polymorph of caffeine. This additional phase was present at different proportions corresponding to the solvent, feedstock concentration and method used. For the three-fluid nozzle method, the feedstock composition was shown to have a large influence on the proportion of co-crystal in the final sample and all three-fluid nozzle samples showed reduced crystallinity compared to the two-fluid nozzle method. The spray dried co-crystals showed resistance to stress conditions over a period of four months and remained detectable following a tableting process. Spray drying is a suitable technique for the preparation of the SAL-CAF co-crystal and with further optimisation of process parameters may be equivalent or superior to milling.