"Batch processing in tanks is the favoured method in industry for manufacture of high-value solid chemicals, such as agrochemicals, dyes and pharmaceuticals. There are a number of disadvantages to batch processing: large amounts of material are committed to each stage; failure can cause loss of the entire batch; there can be large variations in batch repeatability; and it is difficult to scale-up to larger volumes due to limitations on heat flow. Continuous flow manufacture in pipelines offers significant improvements over batch processing: continual processing of small volumes reduces risks in process failures; it is greener technology because it produces less waste; throughput can be increased; capital and running costs are lower; higher surface areas make it easier to heat and cool processes. A grand challenge in implementing continuous flow manufacture is handling of solids, in particular nucleation of fine crystals. Properties of the solid, such as size, shape and internal structure of crystals have enormous effects on their suitability, e.g., as drugs, pesticides, fertilizers. These properties can be difficult to control. Mixing and shear changes the fluid's readiness to grow crystals.
Our research programme aims to improve on current methods for crystallisation in continuous flow by using short, intense pulses of laser light to induce nucleation at specific points and times in the tubes of a continuous flow reactor. So far our laser-induced crystallisation method has been studied in the laboratory using only static sample vials and droplets. We therefore need to study our technique under mixing and flow conditions. Our objective is to demonstrate that our method can grow crystals at different locations where the fluid conditions favour certain crystal shapes, sizes and structures. Such techniques are not already available to industry. Even fractional improvements through this method could yield substantial improvements in the quality of solids, and could encourage industry to switch to continuous flow for more processes. Of course we do not claim that this will be a magic bullet to solve all challenges for continuous manufacture of high-value solids. However, we believe that the technique could stand to make significant savings and improvements in some processes, e.g., in the pharmaceutical industry.
To make our programme relevant to the needs of industry, our project will embark on collaboration with a recently formed consortium for Continuous Manufacture and Crystallisation (CMAC). This group have secured significant investment through government (EPSRC), seven universities, three top-tier global-scale manufacturers (GlaxoSmithKline, AstraZeneca, Novartis), and another 28 industrial partners. CMAC aims to accelerate the adoption of continuous manufacturing processes, systems and plants for the production of pharmaceuticals and fine-chemicals to higher levels of quality, with lower costs, more quickly, and in a more sustainable manner. Our collaboration will ensure that industry leaders have fast and direct access to the outcomes of our research programme."
Short pulses of high power laser light can be used as an external field to induce rapid birth of crystals of various compounds from solutions. We discovered that nanofiltration of such solutions can effectively suppress this effect. This shows that laser-induced nucleation is not just about an interaction of molecules to be crystallised with the laser light but requires additional ingredients that can be removed by nanofiltration.