The objective of this study was to develop a new method for co-crystal preparation which adhered to green chemistry principles, and provided advantages over conventional methods. A novel, solvent-free, high-power ultrasound (US) technique, for preparing co-crystals from binary systems, was chosen as the technology which could fulfil these aims. The application of this technology for solid state co-crystal preparation was explored for ibuprofen-nicotinamide (IBU-NIC), carbamazepine-nicotinamide (CBZ-NIC) and carbamazepine-saccharin (CBZ-SAC) co-crystals. The effect of different additives and processing parameters such as power level, temperature and sonication time on co-crystallisation was investigated. Characterisation was carried out using DSC, PXRD, FTIR, Raman and HPLC. In addition, an NIR prediction model was developed and combined with multivariate analysis (PLS) and chemometric pre-treatments. It was found to be a robust, reliable and rapid method for the determination of co-crystal purity for the IBU-NIC and CBZ-NIC pairs. Co-crystal quantification of US samples helped to optimise the US method. Finally, a model formulation of paracetamol containing 5% and 10% PEG 8000 was ultrasonicated at maximum power with different exposure times. A comparison of technological and physicochemical properties of the resulting tablets with those of the tablets obtained using the pressing method evidenced significant differences. This suggested that US energy dissipation (mechanical and thermal effects) was the main mechanism which caused the PAR form I tabletability to improve. It was found that the ultrasound–compacted tablets released the drug at a slower rate compared to pure PAR. This technique was shown to be useful for improving tabletability for low-compressible drugs without the need to use a conventional tabletting machine.

The objective of this study was to develop a new method for co-crystal preparation which adhered to green chemistry principles, and provided advantages over conventional methods. A novel, solvent-free, high-power ultrasound (US) technique, for preparing co-crystals from binary systems, was chosen as the technology which could fulfil these aims. The application of this technology for solid state co-crystal preparation was explored for ibuprofen-nicotinamide (IBU-NIC), carbamazepine-nicotinamide (CBZ-NIC) and carbamazepine-saccharin (CBZ-SAC) co-crystals. The effect of different additives and processing parameters such as power level, temperature and sonication time on co-crystallisation was investigated. Characterisation was carried out using DSC, PXRD, FTIR, Raman and HPLC. In addition, an NIR prediction model was developed and combined with multivariate analysis (PLS) and chemometric pre-treatments. It was found to be a robust, reliable and rapid method for the determination of co-crystal purity for the IBU-NIC and CBZ-NIC pairs. Co-crystal quantification of US samples helped to optimise the US method. Finally, a model formulation of paracetamol containing 5% and 10% PEG 8000 was ultrasonicated at maximum power with different exposure times. A comparison of technological and physicochemical properties of the resulting tablets with those of the tablets obtained using the pressing method evidenced significant differences. This suggested that US energy dissipation (mechanical and thermal effects) was the main mechanism which caused the PAR form I tabletability to improve. It was found that the ultrasound–compacted tablets released the drug at a slower rate compared to pure PAR. This technique was shown to be useful for improving tabletability for low-compressible drugs without the need to use a conventional tabletting machine.