Crystal engineering study using spray dryer was performed for scale-up and rapid, continuous crystallisation of co-crystals from solution. The study emphasise on developing co-crystals of two structurally similar compounds, caffeine (CAF) and theophylline (THEO) with various di-carboxylic acids. The incongruently soluble pair of CAF and THEO with di-carboxylic acids acquires large solubility difference which is important to consider for its utility in product development. Based on previous assumption that maleic acid (MAL) elevates CAF’s solubility; solubility of the two similar compounds was tested in various dicarboxylic acids. Other solubility enhancement strategies such as introduction of surfactant and binary solvents were also scrutinised. A kinetically similar bench-scale technique, rotary evaporator (rotavap) was investigated as a pre-screening tool for the production of co-crystals via spray drying. Furthermore, various process parameters within the spray dryer were optimised to control the kinetic conditions which influence co-crystallisation and quality of the product. Another polymorphic co-crystal pair, CBZ (carbamazepine) and SAC (saccharin) was examined in various solvents and its degradation was evaluated over a period of few months. In this study, a two-step conversion of CBZ into its degradate was hypothesised. Rotavap delivered a true reflection of co-crystal favoured via spray drying apart from co-crystal pairs depicting polymorphism. Spray dryer offered a unique environment favouring metastable forms of co-crystals irrespective of the starting component stoichiometry; generating CAF:MAL 2:1. However, due to process limitation and solubility constraint, the impurity of CAF in CAF:MAL 2:1 co-crystals could not be abolished.

Crystal engineering study using spray dryer was performed for scale-up and rapid, continuous crystallisation of co-crystals from solution. The study emphasise on developing co-crystals of two structurally similar compounds, caffeine (CAF) and theophylline (THEO) with various di-carboxylic acids. The incongruently soluble pair of CAF and THEO with di-carboxylic acids acquires large solubility difference which is important to consider for its utility in product development. Based on previous assumption that maleic acid (MAL) elevates CAF’s solubility; solubility of the two similar compounds was tested in various dicarboxylic acids. Other solubility enhancement strategies such as introduction of surfactant and binary solvents were also scrutinised. A kinetically similar bench-scale technique, rotary evaporator (rotavap) was investigated as a pre-screening tool for the production of co-crystals via spray drying. Furthermore, various process parameters within the spray dryer were optimised to control the kinetic conditions which influence co-crystallisation and quality of the product. Another polymorphic co-crystal pair, CBZ (carbamazepine) and SAC (saccharin) was examined in various solvents and its degradation was evaluated over a period of few months. In this study, a two-step conversion of CBZ into its degradate was hypothesised. Rotavap delivered a true reflection of co-crystal favoured via spray drying apart from co-crystal pairs depicting polymorphism. Spray dryer offered a unique environment favouring metastable forms of co-crystals irrespective of the starting component stoichiometry; generating CAF:MAL 2:1. However, due to process limitation and solubility constraint, the impurity of CAF in CAF:MAL 2:1 co-crystals could not be abolished.