Control of Crystallisation through the Use of Microemulsions

Abstract

Control of crystallisation is hugely important in many areas of science and technology. The size of crystals can often be crucial in how they perform. In addition the polymorphism of crystals is just as important, especially for the pharmaceutical sciences, where unexpected changes in polymorphism can spell disaster for certain drugs. With these requirements in mind, we have demonstrated that microemulsions can be used to offer thermodynamic control of crystallisation, not just with regards to polymorphism of organic crystals, but also to the synthesis of certain inorganic compounds.
The polymorphism of glycine was first investigated in an attempt to grow all three polymorphs (α-, β- and γ-) at room temperature and pressure. The most stable of these, γ-glycine grows ~ 500 times more slowly than the next most stable form, α-glycine. Using microemulsions made up with the surfactant AOT, the continuous oil phase heptane and a nanoconfined aqueous glycine solution, all three polymorphs of glycine were crystallised by adding methanol dropwise under varying conditions. Non-ionic surfactant systems were also investigated, using combinations of the surfactants Span 80/Tween 80 and Span 80/Brij 30. Using the Span 80/Brij 30 system, the most stable form, γ-glycine, could be formed predominantly by mixing an aqueous glycine microemulsion with an aqueous methanol microemulsion. This proved that Ostwald’s Rule of Stages could be circumvented in order to obtain the most stable polymorph.
Following this, microemulsions were used to demonstrate that inorganic crystalline materials could be synthesised in microemulsion droplets- again at room temperature and pressure. Hydroxyapatite, known as a component of natural bone, was made using Triton X-100/1-hexanol/cyclohexane microemulsions via two methods, firstly via direct addition of reactants, then again via mixed microemulsion methods. Subsequent analysis showed that the final product showed excellent correlation with bought-in hydroxyapatite (reagent grade), with regards to purity and crystallinity.
Finally the synthesis of titanium dioxide nanoparticles was reported. These set of experiments brought both challenges of controlling polymorphism and synthesising materials together. Rutile – the most stable of polymorph of titanium dioxide – was synthesised as the predominant polymorph from the microemulsions. Electron microscopy studies were able to track the particle size growth between 2 and 13 nm at various times up to 18 hours after mixing the reactant microemulsions.