| Summary: | Co-crystallisation is currently a ‘hot topic’ in pharmaceutical development among other fields. Modification of the physicochemical properties of the parent material by inclusion of a second component within the crystal structure, with the potential to lead to large improvements in useful attributes, being the key reason for the interest in co-crystals. Being able to efficiently utilise co-crystallisation to ameliorate problem properties of drugs or other compounds would be a boon to many industries, the pharmaceutical being an ideal example. Limitations in current ability to predict co-crystal formation and potential property modification presents a great opportunity for development in this research area. The work presented in this thesis encompasses the optimisation of a high-throughput ultrasonication based physical co-crystal screen paired with a computational pre-screen, the application of this optimised screen and the analysis of both co-crystalline and co-amorphous materials resulting from the screening. An initial optimisation of a manual physical co-crystal screen was later transferred to an automated screen implemented on a robotics platform. The implementation of the screen and subsequent analysis of products led to the discovery of the stabilisation of an amorphous form of highly polymorphic compound, ROY, through a predicted co-former interaction. The interactions responsible for the stabilisation were further investigated in the ROY:pyrogallol co-amorphous material and it was found that certain analogues of pyrogallol exhibit the same behaviour with ROY depending on the presence and position of specific functionality. Implementation of the optimised co-crystal screen to the antiprotozoal drug ornidazole led to the detection of 23 hits and the crystal structure of the 1:1 co-crystal of ornidazole and 5nitroisophthalic acid being determined by single crystal X-ray diffraction. Characterisation of this co-crystal found that it crystallised much more readily than pure ornidazole, potentially improving its processing characteristics, but that unexpectedly had a lower intrinsic dissolution rate than either of the parent components. In comparison, formulation and characterisation of the already known zafirlukast:piperazine co-crystals showed that large improvements in dissolution rates and oral bioavailability in relation to the parent drug are possible. Specifically, the 1:1 zafirlukast:piperazine co-crystal showed a large increase in dissolution rate in vitro and an accompanying six-fold increase in in vivo oral bioavailability.
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