The research described in this dissertation mainly covers the development of novel technologies for co-crystallisation along with the discovering of plumbagin co-crystal and thermodynamic interrelationship between the co-crystal polymorphs. Co-crystallisation is a fast growing field in the area of crystal design and has shown potential advantages in the field of pharmaceutical. Currently, many research groups are working on the development of new technologies for the synthesis of pure and stoichiometrically controlled co-crystals. In present study, three novel technologies have been developed for co-crystallisation, which include microwave assisted co-crystallisation, spherical crystallisation and microwave assisted sub-critical water processing. The microwave assisted co-crystallisation is a slurry based technology where, effects of drug solubility and dielectric properties of the solvent were investigated using caffeine / maleic acid as a model co-crystal pair. The mechanism of co-crystallisation under microwave irradiation has been proposed. The co-crystals of plumbagin with improved solubility were obtained with the coformers such as hydroquinone, resorcinol and urea using microwave assisted co-crystallisation technique. The spherical crystallisation technology was developed for co-crystallisation of carbamazepine / saccharin co-crystal pair and demonstrated its application for polymorphic control and as a potential technique for the purification of desired crystal form through surface energetic based separation. The thermodynamic interrelationship between Form I and Form II of carbamazepine / saccharin co-crystal was studied using different thermodynamic tests. The results obtained suggest that the carbamazepine / saccharin co-crystal polymorphs are monotropic. Microwave assisted sub-critical water processing has been explored as a green technology for the synthesis of co-crystals. Carbamazepine / saccharin co-crystal pair has been used as a model pair and effects of processing variables on the resulting crystal form and degradation of an API have been studied.

The research described in this dissertation mainly covers the development of novel technologies for co-crystallisation along with the discovering of plumbagin co-crystal and thermodynamic interrelationship between the co-crystal polymorphs. Co-crystallisation is a fast growing field in the area of crystal design and has shown potential advantages in the field of pharmaceutical. Currently, many research groups are working on the development of new technologies for the synthesis of pure and stoichiometrically controlled co-crystals. In present study, three novel technologies have been developed for co-crystallisation, which include microwave assisted co-crystallisation, spherical crystallisation and microwave assisted sub-critical water processing. The microwave assisted co-crystallisation is a slurry based technology where, effects of drug solubility and dielectric properties of the solvent were investigated using caffeine / maleic acid as a model co-crystal pair. The mechanism of co-crystallisation under microwave irradiation has been proposed. The co-crystals of plumbagin with improved solubility were obtained with the coformers such as hydroquinone, resorcinol and urea using microwave assisted co-crystallisation technique. The spherical crystallisation technology was developed for co-crystallisation of carbamazepine / saccharin co-crystal pair and demonstrated its application for polymorphic control and as a potential technique for the purification of desired crystal form through surface energetic based separation. The thermodynamic interrelationship between Form I and Form II of carbamazepine / saccharin co-crystal was studied using different thermodynamic tests. The results obtained suggest that the carbamazepine / saccharin co-crystal polymorphs are monotropic. Microwave assisted sub-critical water processing has been explored as a green technology for the synthesis of co-crystals. Carbamazepine / saccharin co-crystal pair has been used as a model pair and effects of processing variables on the resulting crystal form and degradation of an API have been studied.

Surface energetics play a key role in the delivery of a dry powder inhaler formulation into the lungs, as there must be a sufficient balance of adhesive and cohesive forces to allow optimal lung delivery. In this study, measuring the surface energies of a set of single drug and carrier (budesonide or theophylline with either mannitol or lactose) with different levels of surfactant using Inverse Gas Chromatography, and comparing them to their lung deposition performance using a Next Generation Impactor established a relationship between the two. A 1:10 mixing ratio of budesonide with either carrier was found to have the highest FPF. Coating the carriers with 0.05% sodium lauryl sulphate resulted in a further increase in the FPF when using either budesonide or theophylline as the API, and the same results were seen when a sonocrystallised version of the API was substituted for the micronised form. The calculated IGC values then showed that the highest performing formulations had the lowest dispersive energy and total free surface energy. Furthermore, a trend was observed in the work of adhesion (Wa) and work of cohesion (Wc) for each set of formulations depending on which API was chosen, where for the less polar drug (budesonide) a higher Wa/Wc ratio was associated with the highest formulation performance, and for the more polar drug (theophylline) a smaller Wa/Wc ratio was associated with the highest formulation performance, enabling the estimation of lung performance for a set of single drug and carrier using their surface energy data. / Kuwait’s government and the Ministry of Health of Kuwait