Enhanced Crystallisation Control Using Structured Ternary Fluids

A theory of thermodynamic control over crystallisation has been established for both organic and inorganic materials, allowing the most stable polymorphs to be synthesised under ambient conditions. This control arises from the use of surfactant microemulsions, where nanoscale droplets of one phase are suspended in another. Through this, solute may be confined, slowing crystal growth to allow only the most stable nuclei of the most stable polymorph to persist and grow. Structured ternary fluids (STFs) are complex mixtures that, at certain compositions, contain nanostructures similar to those of surfactant microemulsions, often leading to them being described as surfactant-free, or ultra-flexible microemulsions. This thesis reveals that STF nanostructures may be used to achieve a similar degree of thermodynamic control, where STFs comprised of water, octanol and ethanol could selectively grow the most stable polymorph of glycine, γ-glycine, at supersaturations, c/c_sat , of 1.30 – 1.40. These systems were also used to seed bulk crystallisations, exhibiting an excellent correlation between the polymorphic outcome of the STF and seeded products. Moreover, this work shows that STFs have potential for use in polymorph screening. All three ambient temperature polymorphs of glycine were selectively targeted from a single STF by tailoring the glycine supersaturation. Additionally, all four clinically relevant polymorphs of 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile (ROY) were nucleated concomitantly in an STF of toluene, isopropanol and water, using a high supersaturation of c/c_sat = 5.5. This demonstrated that STF-formed nuclei remain spatially separated for extended periods. This allows multiple polymorphs to nucleate and survive even if there are more stable, faster growing polymorphs present elsewhere. Crucially, in bulk solution, crystallisation is governed by a slow nucleation rate and fast crystal growth mechanism that leads to a lack of polymorphic control and can promote amorphous product precipitation. Conversely, in STFs it has been shown that a fast nucleation rate and a slow crystal growth mechanism were exhibited, promoting crystallisation control.