Investigating two-step nucleation in microfluidic supercritical antisolvent process – SUCRINE

Improving the bioavailability of drugs requires the development of crystallisation processes for which the control of size and crystallinity is well mastered. The use of intensified processes such as supercritical antisolvent process in microreactors has allowed us to obtain crystals of a size never before achieved. We now wish to address the problem of the crystallinity of the particles produced. To this end, we will study nucleation and growth from a fundamental point of view in our systems in order to propose solutions for the preferential preparation of amorphous or crystalline materials. Preliminary results have shown that precipitating fluorescent organic nanoparticles (made of molecules whose fluorescence intensity is much higher in the solid state than in solution) first pass through an amorphous state and then crystallise. This suggests that nucleation takes place in two steps rather than one, a phenomenon never studied in supercritical fluids. The objective of the project is therefore to study, by a coupled experimental/simulation approach, the two-step nucleation (non-classical nucleation theory) in supercritical microfluidics in order to control the precipitation of the amorphous or crystalline form of the material. To do this, we will develop fluorescent organic molecules for which the spectral signature will make it possible to finely discriminate the amorphous or crystalline character of the material. These molecules will be shaped in microfluidic chips in order to thermodynamically and spectroscopically characterise the phases obtained. The supersaturation field will be determined with great precision through intensive numerical simulation in order to rationalise its influence on the phase produced. These results will be of major interest for the controlled preparation of solid particles for various applications.