Sujet de Thèse : Élaboration de nanoparticules par cristallisation/précipitation en microémulsion inverse
Elaboration of nanoparticles via crystallization/precipitation using inverse microemulsion

Keywords : emulsion, nanoparticles, crystallization, precipitation, thermodynamics, kinetics, modelling
Place : LAGEP, Laboratoire d’Automatique et de Génie des Procédés, UMR CNRS 5007 – Université Lyon I – CPE Lyon. Campus de La Doua, Villeurbanne, France.
Main supervisor : Denis MANGIN 1
Co-supervisor : Emilie GAGNIERE
Inverse microemulsion is widely used nowadays as “nanoreactors” since they represent a confined medium, which can be a template for the synthesis of nanomaterials. In some cases, an excellent control of the physico-chemical properties of synthesized nanoparticles such as size, size distribution,
morphology, chemical composition and internal microstructure, can be obtained depending on the initial composition of the microemulsion. In particular, the narrow size distribution of the generated nano-objects has to be connected to the monomodal distribution of the nanodroplets whose sizes can be adjusted between 5 and 100 nm. Since many experimental factors strongly impact the kinetics of particle formation and their size distribution, systems and materials require a complete experimental study.
Numerous studies reported in the literature use inverse microemulsion to synthesize several types of nanoparticles, such as metallic nanoparticles, metal oxides and polymeric nanoparticles 2. The process used is of great interest to the pharmaceutical industry. The supersaturation is generally created by chemical reaction (precipitation). Other modes of generation of the supersaturation may also be envisaged, such as crystallization by solvent reversal, or by pH modification. This technique could also be applied to the synthesis of polymorphs and co-crystals.
The aim of the thesis is to study the inverse microemulsion process through different modes of generation of the supersaturation and on different organic indomethacin) and inorganic (iron iodate) model compounds. First of all, the work will have to focus on the thermodynamic aspects of these complex systems. A second part of the thesis will be devoted to the formulation of stable inverse microemulsions.
After that, an experimental study in agitated reactor will be carried out in order to identify the key parameters of the process and their influences on the chemical, physico-chemical and colloidal properties of the obtained nanoparticles, and on the polymorphic form generated. The results will then be used to develop and adjust a mass transfer model. Modelling is essential to point out and decouple the effects of different mechanisms and to interpret the experimental results.
This thesis is based on previous works carried out at the LAGEP in the field of microemulsions in the GEPHARM team 3 4 and in solid engineering in the PES team 5 6(crystallization, co-crystallization, precipitation, polymorphism).

1. E-mail : firstname.lastname@univ-lyon1.fr
2. B.L. Cushing, V.L. Kolesnichenko, C.J. O’Connor, Recent Advances in the Liquid-Phase Syntheses of Inorganic Nanoparticles, Chemical Reviews, 2004, 104,3893-3946.
3. R. Ladj, A. Bitar, M. Eissa, Y. Mugnier, R. Le Dantec, H. Fessi, A. Elaissari, Individual inorganic
nanoparticles : preparation functionalization and in vitro biomedical diagnostic applications, Journal of Materials
Chemistry B, 2013, 1, 1381-1396.
4. R. Ladj, M. El Kass, Y. Mugnier, R. Le Dantec, H. Fessi, C. Galez, A. Elaissari, SHG Active Fe(IO3)3
Particles : from spherical nanocrystals to urchinlike microstructures through the additive-mediated microemulsion
route, Crystal Growth and Design, 2012, 12, 5387-5395.
5. E. Gagnière, D. Mangin, F. Puel, A. Rivoire, O. Monnier, E. Garcia, J.P. Klein, Formation of co-crystals :
kinetic and thermodynamic aspects, Journal of Crystal Growth, 2009, 311, 2689-2695
6. D. Mangin, F. Puel, S. Veesler, Polymorphism in processes of crystallization in solution : a practical review,
Organic Process Research and Development, 2009, 13, 1241-1253.