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Procédés et Fluides Supercritiques

Extraction supercritique

Fractionnement supercritique

Génération de particules, cristallisation, encapsulation

Imprégnation (matrices et implants polymériques, silices, …)

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Procédés et fluides supercritiques
Présentation

Les fluides supercritiques (FSC) ou sous critiques ont des propriétés spécifiques qui sont exploitées dans un certain nombre d'applications aussi bien à l'échelle du laboratoire qu'à l'échelle industrielle. Leur utilisation représente une alternative à l'utilisation des solvants organiques présentant des problèmes de pollution, de toxicité et/ou de sécurité. 

L’équipe «Procédés & Fluides Supercritiques» possède une expertise particulière scientifique et technologique permettant la conception, la conduite et l’optimisation de procédés utilisant le CO2 supercritique. 
Pour une meilleure maîtrise de ces procédés, une approche multi-échelle est privilégiée. L’équipe étudie plus particulièrement les propriétés des fluides supercritiques, les équilibres de phase, les phénomènes aux interfaces et les transferts au sein de ces milieux sous pression. Une attention particulière est également portée aux comportements de matériaux, aussi bien d’origine synthétique que biologique, en contact avec du dioxyde de carbone supercritique.
Des outils de modélisation développés au sein de l’équipe permettent d’appréhender plus particulièrement les cinétiques de transfert (écoulements, phénomènes de dispersion, mélange) et la thermodynamique de ces milieux sous pression. 

L’équipe a une activité forte centrée sur les applications suivantes :
- Extraction supercritique, fractionnement supercritique et mise en forme de produits d’origine végétale
- Élaboration de systèmes à libération contrôlée médicamenteux (cristallisation de principes actifs, encapsulation, imprégnation,…)
- Stérilisation supercritique de dispositifs médicaux et produits de santé
- Dé-cellularisation supercritique de greffons


Partenaires industriels (période 2020-2024) : 

BioTechOne ; Cousin Surgery ; Lattice Medical ; Le Rouge Français ; Solvay ; Symrise ; THEA ; Total Energies


+ Extraction supercritique
+ Fractionnement supercritique
+ Génération de particules, cristallisation, encapsulation
+ Imprégnation (matrices et implants polymériques, silices, …)

Responsable

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Annuaire personnel permanent

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Doctorants, Post-Doctorants et CDD

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Equipement

- Autoclaves d'extraction, de cristallisation et d'imprégnation - de quelques mL à plusieurs litres.
- Montage expérimental de cristallisation ou d'encapsulation en milieu supercritique.
- Pilote de fractionnement supercritique
- Autoclave à fenêtre
- Cellules Haute Pression de mesures d'équilibres de phases résistant jusqu'à 700 bar. 

Dernières publications de l'équipe

  • 2025
    Zohra Laggoune, Yasmine Masmoudi, Seyed Ali Sajadian, Elisabeth Badens. Sirolimus solubility in supercritical carbon dioxide: Measurement and modeling.. Journal of CO2 Utilization, 2025, 93, pp.103034. ⟨10.1016/j.jcou.2025.103034⟩. ⟨hal-04954883⟩ Plus de détails...

    Sirolimus solubility in supercritical carbon dioxide: Measurement and modeling.

    The solubility of drugs in supercritical carbon dioxide is a key parameter in their processing. This study focuses on sirolimus, an immunosuppressive drug used in organ transplantation. Its solubility in supercritical carbon dioxide was measured using a static gravimetric method. Measurements were carried out at pressures ranging from 12.5 MPa to 25.0 MPa and temperatures from 313 K to 328 K. The findings revealed a molar fraction range of sirolimus between 1.20 × 10 6 and 2.73 × 10 6 and a direct solubility behavior in the investigated domain. The experimental data were correlated using several models. These included semi-empirical density-based models (Chrastil, Mendez-Santiago and Teja, Bartle et al., Kumar and Johnston, Sparks et al., and Sodeifian et al.), as well as equation of state-based models (Soave-Redlich-Kwong and Peng-Robinson). The results indicated that Sparks et al. and Soave-Redlich-Kwong showed the lowest average absolute relative deviation (AARD%) and the corrected correlation coefficient (Radj) of 4.12 %, 0.978 and 05.18 %, 0.980 respectively.
    Zohra Laggoune, Yasmine Masmoudi, Seyed Ali Sajadian, Elisabeth Badens. Sirolimus solubility in supercritical carbon dioxide: Measurement and modeling.. Journal of CO2 Utilization, 2025, 93, pp.103034. ⟨10.1016/j.jcou.2025.103034⟩. ⟨hal-04954883⟩
    Journal: Journal of CO2 Utilization
    Date de publication: 01-03-2025
    Auteurs:
    Digital object identifier (doi): http://dx.doi.org/10.1016/j.jcou.2025.103034
    Voir la publication sur Hal
  • 2024
    Adil Mouahid, Magalie Claeys-Bruno, Sébastien Clercq. A New Methodology Based on Experimental Design and Sovová’s Broken and Intact Cells Model for the Prediction of Supercritical CO2 Extraction Kinetics. Processes, 2024, 12 (9), pp.1865. ⟨10.3390/pr12091865⟩. ⟨hal-04791947⟩ Plus de détails...

    A New Methodology Based on Experimental Design and Sovová’s Broken and Intact Cells Model for the Prediction of Supercritical CO2 Extraction Kinetics

    Nowadays, supercritical CO2 extraction is highly regarded in industry, and several studies dealing with scale-up calculations aim to facilitate the transition from small scale to large scale. To complete this transition, it would be interesting to be able to predict supercritical CO2 extraction kinetics, which is the aim of this work. A new methodology based on the association of Sovová’s broken and intact cell model and response surface methodology was developed to predict SC-CO2 extraction kinetics from different biomass (Argan kernels, evening primrose, Punica granatum, Camellia sinensis, and dry paprika) at different operating conditions (200–700 bar, 40–60 °C, 0.14–10 kg/h) inside an operating domain. The absolute average relative deviations between the experimental and predicted data ranged from 1.86 to 29.03%, showing satisfactory reliability of this new methodology.
    Adil Mouahid, Magalie Claeys-Bruno, Sébastien Clercq. A New Methodology Based on Experimental Design and Sovová’s Broken and Intact Cells Model for the Prediction of Supercritical CO2 Extraction Kinetics. Processes, 2024, 12 (9), pp.1865. ⟨10.3390/pr12091865⟩. ⟨hal-04791947⟩
    Journal: Processes
    Date de publication: 31-08-2024
    Auteurs:
    Digital object identifier (doi): http://dx.doi.org/10.3390/pr12091865
    Voir la publication sur Hal
  • 2024
    Aymeric Fabien, Guillaume Lefebvre, Elisabeth Badens, Brice Calvignac, Damien Chaudanson, et al.. Contact angle of ethanol, water, and their mixtures on stainless steel surfaces in dense carbon dioxide. Journal of Colloid and Interface Science, 2024, 655, pp.535-545. ⟨10.1016/j.jcis.2023.10.163⟩. ⟨hal-04316090⟩ Plus de détails...

    Contact angle of ethanol, water, and their mixtures on stainless steel surfaces in dense carbon dioxide

    Hypothesis Contact angle can be a key parameter in chemical engineering. However, the development and the optimization of numerous processes using supercritical CO2, considered as environmentally friendly, requires new measurements under dense CO2 atmosphere. Besides, the influence of the roughness or the wetting regime on the contact angle is known at ambient conditions but remains to be discussed for systems under high pressure. Experimental Contact angle measurements of ethanol, water, and their mixtures, with ethanol mass fractions ranging from 0.25 to 0.75, on two stainless steels in saturated CO2 at pressures ranging from 0.1 MPa to 15.1 MPa, and at 313 K and 333 K were carried out in a set-up improving mass transfer between the studied liquid and the continuous fluid phase. Stainless steel surfaces have been characterized by atomic force and scanning electron microscopies allowing the application of the Wenzel equation. Findings Ethanol wetted totally both stainless steels while contact angles of all other liquids were increased by the rise of pressure, with contact angles up to 128 ° for water at 15.1 MPa. Trapped bubbles were observed at the solid/liquid interface and the bubble formation is discussed. Furthermore, the potential influence of bubble presence on the wetting regime is prospected through the question: could the pressure rise modify the wetting regime?
    Aymeric Fabien, Guillaume Lefebvre, Elisabeth Badens, Brice Calvignac, Damien Chaudanson, et al.. Contact angle of ethanol, water, and their mixtures on stainless steel surfaces in dense carbon dioxide. Journal of Colloid and Interface Science, 2024, 655, pp.535-545. ⟨10.1016/j.jcis.2023.10.163⟩. ⟨hal-04316090⟩
    Journal: Journal of Colloid and Interface Science
    Date de publication: 01-02-2024
    Auteurs:
    Liste des documents:
    Digital object identifier (doi): http://dx.doi.org/10.1016/j.jcis.2023.10.163
    Voir la publication sur Hal
  • 2024
    Adil Mouahid, Catherine Rébufa, Yveline Le Dréau. Supercritical CO2 extraction of Walnut (Juglans regia L.) oil: Extraction kinetics and solubility determination. Journal of Supercritical Fluids, 2024, 211, pp.106313. ⟨10.1016/j.supflu.2024.106313⟩. ⟨hal-04587482⟩ Plus de détails...

    Supercritical CO2 extraction of Walnut (Juglans regia L.) oil: Extraction kinetics and solubility determination

    Experimental and modelling investigations of supercritical CO2 extraction of oil from Juglans regia L. kernels were conducted at 200 and 400 bar, 313 and 333 K at a CO2 flow rate of 0.1 kg/h. Regardless of the pressure and the temperature, the highest achievable yield was estimated at about 0.7 kgoil / kgbiomass. The extraction kinetics were modeled with Sovov´a’s broken and intact cells model. Walnut oil apparent solubility in supercritical CO2 was determined and modelled with the Chrastil equation. A retrograde solubility behaviour was observed at 200 bar, the faster extraction kinetics were found at 400 bar and 333 K. The fatty acid composition of the supercritical CO2 extracted oil was compared to the quality of the oil extracted by press and n-hexane Soxhlet extraction.
    Adil Mouahid, Catherine Rébufa, Yveline Le Dréau. Supercritical CO2 extraction of Walnut (Juglans regia L.) oil: Extraction kinetics and solubility determination. Journal of Supercritical Fluids, 2024, 211, pp.106313. ⟨10.1016/j.supflu.2024.106313⟩. ⟨hal-04587482⟩
    Journal: Journal of Supercritical Fluids
    Date de publication: 01-01-2024
    Auteurs:
    Liste des documents:
    Digital object identifier (doi): http://dx.doi.org/10.1016/j.supflu.2024.106313
    Voir la publication sur Hal
  • 2023
    Vénicia Numa, Christelle Crampon, Arnaud Bellon, Adil Mouahid, Elisabeth Badens. Valorization of food side streams by supercritical fluid extraction of compounds of interest from apple pomace. Journal of Supercritical Fluids, 2023, 202, pp.106056. ⟨10.1016/j.supflu.2023.106056⟩. ⟨hal-04543465⟩ Plus de détails...

    Valorization of food side streams by supercritical fluid extraction of compounds of interest from apple pomace

    Supercritical CO2 (scCO2) extraction, a green technology still little applied to side streams, has been used to explore the potential recovery of beneficial compounds from apple pomace, a food industry byproduct. The study examines the potential of scCO2 extraction on freeze-dried and airflow dried apple pomace, using laboratory-scale equipment with varying pressures (200–400 bar), temperatures (35–55 °C) with a fixed CO2 flow rate. Extracts were analyzed through LC-MS and GC-MS, while antioxidant capacity was assessed using the ABTS assay. The results were compared to those from Soxhlet n-hexane extraction. Optimal conditions of 300 bar and 55 °C with freeze-dried apple pomace yielded the highest mass loss. The main compounds identified included glyceryl dilinoleate, linoleic acid, and diacyl glycerol, with significant ursolic acid content. A preliminary higher scale feasibility test under optimal conditions demonstrated promising, duplicable outcomes, supporting prior claim that apple pomace contains valuable ingredients that can be reused in various industrial sectors.
    Vénicia Numa, Christelle Crampon, Arnaud Bellon, Adil Mouahid, Elisabeth Badens. Valorization of food side streams by supercritical fluid extraction of compounds of interest from apple pomace. Journal of Supercritical Fluids, 2023, 202, pp.106056. ⟨10.1016/j.supflu.2023.106056⟩. ⟨hal-04543465⟩
    Journal: Journal of Supercritical Fluids
    Date de publication: 01-11-2023
    Auteurs:
    Liste des documents:
    Digital object identifier (doi): http://dx.doi.org/10.1016/j.supflu.2023.106056
    Voir la publication sur Hal
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Rencontres scientifiques

Archives récentes Archives

Soutenances de thèses et HDR

Archives récentes
25 novembre 2024 - Design and optimization of supercritical treatment processes for interventional cardiology medical devices / Zohra Laggoune PhD Defense
Doctorante : Zohra Laggoune

Date : 25 novembre à 14h00, Cerege amphi Technopôle de l'Arbois-Méditerranée

Abstract: Atherosclerosis, a leading cardiovascular condition, involves arterial narrowing due to fatty deposits, impeding blood flow. Angioplasty, using stents or balloons, is a minimally invasive treatment for atherosclerosis. Recent advances have led to the development of active stents and balloons, which release antiproliferative agents (e.g., sirolimus) via a polymeric coating to prevent restenosis and promote arterial healing. Conventionally, these devices are manufactured using organic solvents, and may then contain harmful residues posing environmental and health concerns.
This thesis, conducted in collaboration with AlchiMedics, investigates supercritical CO2 technology as an eco-friendly alternative for manufacturing active coronary medical devices. The study first focuses on the behavior of the polymers that compose them in a supercritical CO2 environment. A Fourier Transformed InfraRed microscope coupled with a high-pressure cell was used to measure CO2 sorption in the polymers and their swelling. Additionally, a high-pressure visualization cell was used to assess the physical state of the polymers when exposed to supercritical CO2. Furthermore, the solubility in supercritical CO2 of sirolimus, the main active ingredient involved in this thesis, was determined using a static gravimetric method, followed by data modeling.
Based on this fundamental knowledge, supercritical CO2 was applied to extract residual solvent from pre-dried active stents (HT Supreme®). Semi-continuous mode extraction at 8 MPa, 308.15 K for 0.5 h resulted in an extraction efficiency of 91.80 % while minimizing polymer detachment and ensuring satisfactory in-vitro sirolimus release.
This study also explores supercritical impregnation of sirolimus to develop active balloons and stents, targeting a drug loading of 1.2 µg.mm-2 for both devices. Balloon impregnation was performed in batch mode based on a Design of Experiments. Operating conditions of 18 MPa, 323.15 K for a duration of 18 h were identified to maximize the drug loading to 0.68 µg.mm-2, while achieving positive ex-vivo results. In contrast, impregnations of two types of commercial stents (AMS® and HT Supreme®) resulted in low drug loadings and detachment of polymeric coatings. The development of the Fast Impregnation process (FIP), significantly improved drug loadings from 0.035 to 1.11 µg.mm-2 for AMS®, and from 0.015 to 7.3 µg.mm-2 for HT Supreme®. This process also preserved the integrity of polymer coatings under conditions set at 12.5 MPa and 308.15 K for AMS®, and at 25 MPa and 313.15 K for HT Supreme®.

Keywords: Atherosclerosis, active coronary stent, active coronary balloon, polymers, supercritical CO2, impregnation, extraction, sterilization

Jury :
Pr. Albertina CABAÑAS - Complutense University of Madrid - Reviewer
Pr. Iolanda DE MARCO - University of Salerno -  Reviewer
Dr. Thierry TASSAING - University of Bordeaux- Examiner and president of the jury
Pr. Loïc MACÉ - Aix Marseille University - Examiner
Pr. Elisabeth BADENS -  Aix Marseille University - Thesis director 
Dr. Yasmine MASMOUDI - Aix Marseille University - Thesis co-director
Dr. Christophe BUREAU - AlchiMedics - Thesis co-director and guest member 
24 septembre 2024 - Supercritical technology applied to the development of innovative intravitreal sustained-release drug delivery systems / Matthieu Schneider PhD defense
Doctorant : Matthieu SCHNEIDER

Date : le 24 septembre à 9h00, amphithéâtre du CEREGE, technopole de l'Arbois

Abstract : Age-related macular degeneration (AMD), manifested by the appearance of a dark spot in the center of the vision, has become a significant public health issue, with the number of patients set to rise over the coming decades. Since 2006, the pharmaceutical industry has introduced therapies with monthly intravitreal injections of anti-VEGF (vascular endothelial growth factor) antibodies to mitigate its development. Designing an intravitreal implant with antibody release controlled over twelve weeks has been proposed to simplify therapy management. Antibodies are thermally, chemically, and biologically sensitive therapeutic proteins. This study demonstrates the potential of the Sequential Dispersion Particles from Gas Saturated Solution (SD-PGSS) process for encapsulating sensitive active ingredients. The SD-PGSS process enables work to be carried out at moderate temperatures (38 °C) and without solvent. The study focused on the optimization of operating conditions through the investigation of polyesters (Polycaprolactone PCL, poly(Lactide-co-Glycolide) PLGA, and a polyether (Poly(Ethylene Glycol) PEG) biocompatible in the presence of supercritical CO2. Two operating conditions were selected: 38 °C/25 MPa for PCL and the PCL/PLGA blend (1:1 w/w) and 45 °C/25 MPa for PCL alone and the PCL/PEG blend (1:1 w/w). The implementation of the SD-PGSS process resulted in a repeatable process with high yields (80 - 95%). The study of two model molecules, lutein, a small hydrophobic molecule of therapeutic interest studied in an oral administration context, and bovine serum albumin, a hydrophilic protein studied in an intravitreal release scenario, demonstrated the repeatability of the process, the homogeneity of the final product, and the possibility of modulating the release in vitro. The antibody study demonstrated low activity maintenance and prolonged release for up to 8 weeks, leading to a prototype with compatible dimensions for ophthalmic use.

Jury
Géraldine PIEL                         Rapporteuse / Professeure, Université de Liège, Belgique
Ernesto DI MAIO                      Rapporteur / Professeur, Université de Naples-Federico II, Italie
Martial SAUCEAU                    Examinateur / Maître-assistant, Ecole des Mines d’Albi-Carmaux
John CONRATH                       Président du jury / Professeur - Chirurgien, Clinique Monticelli 
Elisabeth BADENS                   Directrice de thèse / Professeure, Aix-Marseille Université 
Yasmine MASMOUDI               Co-directrice de thèse / Maître de conférences , Aix-Marseille Université
Frédéric MATONTI                   Membre invité / Professeur - Chirurgien , Clinique Monticelli
Céline OLMIERE                      Membre invitée / Directrice scientifique, Théa Open Innovation