Pervaporation membranaire pour la cristallisation : Développement d’un procédé continu en génie pharmaceutique

Thesis supervisor: Catherine CHARCOSSET: catherine.charcosset@univ-lyon1.fr
Thesis co-supervisors: Élodie CHABANON: elodie.chabanon@univ-lyon1.fr
Denis MANGIN: denis.mangin@univ-lyon1.fr

Subject description:
The crystallization/precipitation of a compound is generated under a change of temperature and/or composition (solvent evaporation, antisolvent addition, seeding…) of a saturated solution. Hence, a fine control of heat transfer and/or of mass transfer is a key parameter of the unit process. Besides, membrane processes are considered as one of the most promising technology in order to develop an intensified (volume/cost decrease, production/purity increase…), continuous, easy to scale up process allowing a fine local control of hydrodynamics and mass/heat transfer.
Amongst the membrane processes knowing a growing interest, the membrane pervaporation process is mainly used to dehydrate solvents and separate organic mixtures. The aim is to use a dense membrane (without pores) on the surface of which a liquid phase, usually heated, is flowing. The other side of the membrane (i.e., the permeat side) is under vacuum allowing the mass transfer through the membrane by vaporization of a preferential compound. In pharmaceutics, membrane pervaporation is mainly used to the dehydration of effluents in order to recover solvents, to eliminate water during chemical reactions and to the crystallization by solvent evaporation. However, this last technique remains low investigate despite the industrial potentialities to develop an intensified process.

The aims of this thesis are:
i. to develop a lab-scale pilot of membrane pervaporation;
ii. to highlight the influence of the operating and geometrical parameters (membrane materials, flowrate, etc.) on the separation of a model mixture (for example: water/ethanol), then on the crystallization of a model compound (for example: paracetamol);
iii. to use the results obtained to the separation of several mixtures and to the crystallization of active principles; a particular attention will be brought to the highlight of the potentialities (supersaturation control, polymorphism control…);
iv. to develop a continuous process for industrialization (for example by using several membrane modules in series) and a predictive model of membrane pervaporation.

This thesis is part of the continuity of research carried out at LAGEP in the field of membrane processes in pharmaceutical engineering and particulate solids processing (crystallization, cocrystallization, precipitation, polymorphism).

References:
E. CHABANON, D. MANGIN, C. CHARCOSSET, Membranes and crystallization processes: State of the art and prospects, Journal of Membrane Science, 509 (2016) 57-67.
R. KIEFFER, D. MANGIN, F. PUEL, C. CHARCOSSET, Precipitation of Barium sulphate in a hollow fiber membrane contactor, Part II: the influence of the process parameters, Chemical Engineering Science, 64 (2009) 1885-1891.
P.D. CHAPMAN, T. OLIVEIRA, A.G. LIVINGSTON, K. LI, Membranes for the dehydration of solvents by pervaporation, Journal of Membrane Science, 318 (2008) 5–37.
D. CHEN, K.K. SIRKAR, C. JIN, D. SINGH, R. PFEFFER, Membrane-based technologies in the pharmaceutical industry and continuous production of polymer-coated crystals/particles, Current Pharmaceutical Design, 23 (2017) 242-249.
X. ZHANG, C. LI, X. HAO, X. FENG, H. ZHANG, H. HOU, G. LIANG, Recovering phenols as high purity crystals from dilute aqueous solutions by pervaporation, Chemical Engineering Science, 108 (2014) 183-187.Thesis supervisor: Catherine CHARCOSSET: catherine.charcosset@univ-lyon1.fr
Thesis co-supervisors: Élodie CHABANON: elodie.chabanon@univ-lyon1.fr
Denis MANGIN: denis.mangin@univ-lyon1.fr

 

Filed under: Recrutement, Sujet(s) de Thèse