Thesis (M.S.P.)--University of Toledo, 2004. / Typescript. "A thesis [submitted] as partial fulfillment of the requirements of the Master of Science degree in Pharmaceutical Sciences." Bibliography: leaves 94-112.

Dispersing co-crystals in a polymeric carrier may improve their physicochemical properties such as dissolution rate and solubility. Additionally co-crystal stability may be enhanced. However, such dispersions have been little investigated to date. This study focuses on the feasibility of dispersing co-crystals in a polymeric carrier and theoretical calculations to predict their stability. Acetone/chloroform, ethanol/water, and acetonitrile were used to load and grow co-crystals in a HPMCAS film. Caffeine-malonic acid and ibuprofennicotinamide co-crystals were prepared using solvent evaporation method. The interactions between each of the co-crystals components and their mixtures with the polymer were studied. A solvent evaporation approach was used to incorporate each compound, a mixture, and co-crystals into HPMCAS films. Differential scanning calorimetry data revealed a higher affinity of the polymer to acidic compounds than their basic counterparts as noticed by the depression of the glass transition temperature (Tg). Moreover, the same drug loading produced films with different Tgs when different solvents were used. Solubility parameter values (SP) of the solvents were employed to predict that effect on the depression of polymer Tg with relative success. SP values were more successful in predicting the preferential affinity of two acidic compounds to interact with the polymer. This was confirmed using binary mixtures of naproxen, flurbiprofen, malonic acid, and ibuprofen. On the other hand, dispersing basic compounds such as caffeine or nicotinamide with malonic acid in HPMCAS film revealed the growth of co-crystals. A dissolution study showed that the average release of caffeine from films containing caffeine-malonic acid was not significantly different to that of films containing similar caffeine concentration. The stability of the caffeine-malonic acid co-crystals in HPMC-AS was prolonged to 8 weeks at 95% relative humidity and 45°C. The theory developed in this project, that an acidic drug with a SP value closer to the polymer will dominate the interaction process and prevent the majority of the other material from interacting with the polymer, may have utility in designing co-crystal systems in polymeric vehicles

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.