Etude expérimentale et modélisation du procédé de granulation humide

Laboratoire : Laboratoire d’Automatique et Génie des Procédés (LAGEP, UMR CNRS 5007) – Equipe Procédés d’Elaboration du Solide et Equipe Génie Pharmacotechnique
Coordonnées: LAGEP, Université Lyon 1, 43 Bd du 11 novembre 1918, Bâtiment CPE-308G, 69622 Villeurbanne Cedex,
Contact : claudia.cogne@univ-lyon1.fr, +33 (0)4 43 72 18 55
Encadrants : Claudia Cogné (direction), Sandrine Bourgeois (co-encadrement)

Description:
Context
Wet granulation is a process encountered in many industries (pharmaceutical, chemical, food) to produce granules with desired properties from fine powder. During high-shear granulation, a binder solution is added to the mechanically blended powder mix which results in particle size enlargement by the formation of liquid bridges between primary particles. A typical high shear granulation experiment implies a premixing of the initial dry powder, the addition of the liquid binder and the drying step. This work will focus on the first two stages.
Wet granulation is primarily used to improve the physical and rheological properties of the powder and therefore to facilitate handling and further processing. The control of the process is required especially in pharmaceutical field, to improve reproducibility, to achieve acceptable drug content uniformity and to ensure product stability.

Previous works

Amongst the recent studies, the bibliographic review underlines the complex particle design process that could be summarized in three points:
• Wet granulation is commonly described as a combination of three steps [1]: (i) wetting and nucleation, (ii) consolidation and growth by coalescence and (iii) attrition and breakage. Studies are commonly focused on the investigation of one predominant mechanism. But the ability to predict the intensity of the different granulation mechanisms and their interactions is difficult.
• Systematic studies [2-3] have been carried out to investigate correlations between operating conditions (fill ratio, impeller speed, chopper presence …), physico-chemical properties of the binder solution (wettability, contact angle, viscosity …) and granules quality (size, distribution, flowability, homogeneity …). But the effect of the operating parameters on the granulation mechanisms is highly dependent on the raw materials (particles size, porosity…) and on the technology, which make difficult the scalability and the optimization of the process.
• In recent years, research efforts have been complemented by computer simulations. Modelling approaches for wet granulation processes that can be loosely separated into two categories [4]: (i) Empirical models based on adimensional numbers determination are often limited to a specific application and can hardly be extended toward other granulation processes; (ii) Population balance models provide a more fundamental framework for tracking changes in particle properties over time, though they require empirical parameters that cannot easily be measured and neglect the flow pattern of powder.

Objective
The main objective of this project is to develop more fundamental scientific knowledge and experimental data set to understand the interactions between the intrinsic characteristics of a powder, physico-chemical properties of the binder, process parameters and the final quality of the produced granules. The significant number of parameters making the experimental study rather important, an approach by the numerical simulation will be also developed. So, the program of this study could be divided in two parts:
(1) An experimental investigation in order to study and to control the interparticle force effects and the physico-chemical characterization of the interfaces. Moreover, the produced granules will be characterized in term of size distribution, porosity, surface, mechanical resistance and flowability.
(2) The development of a multi-scale model taking into account the flow pattern of particles to predict the size distribution of particles. The Discrete Element Method (DEM) seems to be the ideal approach. Firstly, it allows tracking particles as they move through space and collide, in order to identify key parameters that affect the quality of the mixture and the segregation of particles. Secondly, it allows the integration of complex interactions between particles, such as cohesion or breaking forces by taking into account variables such as the collisions frequency or particles relative velocities. As the Discrete Element Method is known to be computationally expensive, an alternative solution could be the development of an hybrid model by coupling DEM with population balance model. This could be done by dividing the simulation domain into multiple compartments with each of them having its own agglomeration kinetics.

Particular skills develop during the PhD multidisciplinary skills (experimentation, powder characterization, modeling), knowledge and use of various techniques and equipment (high shear granulator, powder flow analyzer, annular shear cell) and development of multi-scale model such as DEM, should allow to the PhD student to improve specific knowledge in process engineering and pharmaceutical technology.

Candidate profile:
Engineer in chemical engineering or equivalent with a master degree. Experience in the field of modeling will be advisable.

Références
[1] Saleh K., Guigon P. (2009) Mise en oeuvre des poudres – Techniques de granulation et liants, Techniques de l’Ingénieur, J2 254.
[2] Chitu T. et al., (2011) Effect of chopper presence, design and impeller speed, Powder Technology, 206 (1-2), 34-43.
[3] Smirani-Khayati N. et al., (2009) Binder liquid distribution during granulation process and its relationship to granule size distribution, Powder Technology, 195 (2), 105-112.
[4] Bouffard J. et al., (2012) A multiscale model for the simulation of granulation in rotor-based equipment, Chemical Engineering science, 81, 106-117.
Laboratoire : Laboratoire d’Automatique et Génie des Procédés (LAGEP, UMR CNRS 5007) – Equipe Procédés d’Elaboration du Solide et Equipe Génie Pharmacotechnique
Coordonnées: LAGEP, Université Lyon 1, 43 Bd du 11 novembre 1918, Bâtiment CPE-308G, 69622 Villeurbanne Cedex,
Contact : claudia.cogne@univ-lyon1.fr, +33 (0)4 43 72 18 55
Encadrants : Claudia Cogné (direction), Sandrine Bourgeois (co-encadrement)

 

Filed under: Recrutement, Sujet(s) de Thèse