Powder processing using supercritical fluids

International audienceParticulate solids attract a lot of industrial interest as they are used so widely, particularly in the agro-food, pharmaceutical, cosmetics and mineral industries. However they are also the focus of a lot of scientific attention while their generation, their formulation and the control of their usage properties are still not well understood and mastered. In the domain of particle formation, processes using crystallisation from a supercritical medium constitute a new route to obtain finely divided solids. By using pressure as an operating parameter, these processes lead to the production of fine and monodisperse powders. Previously to the study of the processes, it is necessary to know the solubility of the studied solids in supercritical phases which require the knowledge of the behaviour of the different fluid and solid phases involved.There exist two families of processes, according to whether supercritical fluid - usually carbon dioxide - is used as a solvent or an anti-solvent: RESS or SAS. In the first case it is the drop in density due to the sudden decompression of the fluid, which is the driving force of nucleation. Because of its simplicity, RESS remains the first process to be tested and a large amount of different materials have been processed through RESS and its derivatives. Its main limitation lies in the rather poor solubility of several families of molecules in carbon dioxide.In the SAS process, it is the reciprocal dissolution of an organic solvent in the supercritical fluid which leads to the particle precipitation. The universality of SAS (there is always a proper solvent-antisolvent couple for the studied solute) will ensure future developments for very different type of materials. Very often, semi-continuous SAS process and RESS process can compete for pre-industrial particle generationSupercritical-assisted particle formation has made a lot of progress in the recent years. Both RESS and SAS processes continue to undergo fundamental and applied research and have benefited from the recent years’ advances. Even if several controversial issues are still in debate in the scientific community, industrial applications are expected soon in many sectors, though it is the pharmaceutical industry which seems best equipped to gather a majority of its developments

Sainte-Enimie – Le tumulus du Devez Viel

Date de l'opération : 1991 - 1992 (SU) ; 1993 (SU) Inventeur(s) : Fages Gilbert (SRA) ; Vacquier Jacques Sur le causse de Sauveterre et au nord-est du hameau du même nom, le site archéologique du Devez Viel occupe l’aire sommitale d’une croupe dominante. L’altitude du replat supérieur est comprise entre 1 010 m et 1 050 m. Cette sorte de petit plateau est structuré par deux modelés karstiques (sotch) distants d’une centaine de mètres. Il livre en surface quelques tessons érodés et des pièces ..

Modelling solid solubilities in SC-CO2 and cosolvent : development of enhanced density-based models

International audienceThe solubility of a solid of pharmaceutical interest in supercritical carbon dioxide, with or without cosolvent has been measured by means of a novel apparatus. This solubility data has been correlated by means of several density–based semi–empirical models, which have been extended and modified to be applicable to mixtures with cosolvent

Supercritical carbon dioxide : an efficient tool for the production of ultra-fine particles for the food and pharmaceutical industries

International audienceThe agro-food, pharmaceutical, cosmetics and detergent industries are among the greatest users of particulate solids, or powders. It is hardly necessary, therefore, to expound their industrial importance. However, there is still plenty of room for development, as their generation, their formulation and the control of their usage properties are yet to be fully mastered.In the domain of particle formation, there are traditionally two main ways of obtaining divided solids, depending on whether the base material is in the solid or liquid state: crushing, milling, comminution belong to the former category while crystallisation, precipitation, spray-drying and atomization belong to the latter. Obtaining powders by processes using supercritical fluids is a third route, which has undergone significant development during the last decade. By using pressure as an operating parameter, these processes lead to the production of fine and monodisperse powders. There exist three families of processes (RESS, SAS and PGSS) according to the way in which the FSC - generally CO2 - is used.•In the RESS process, CO2 is the solvent and it is the fall of density related to a rapid depressurisation which promotes the nucleation of the solute. Although it is easy to implement, this process is however limited by the relatively tight spectrum of CO2-solvent properties. •In the SAS process, CO2 is used as a non (or anti)-solvent and it is the reciprocal dissolution of an organic solution and the supercritical fluid which causes precipitation. The great versatility of SAS remains its principal advantage. •Lastly, in the PGSS process, the dissolution of CO2 into an organic solution or a molten polymer, is followed by an abrupt depressurisation in which the dissolved gas acts as an aerosol generator helping the particle formation. This process is particularly advisable for polymer coating applications.In this paper, two examples of application of these processes are described.A high-value foodstuff, cocoa butter has been crystallised in a specific polymorph. The particles produced can be used to improve tempering, a key-stage in the chocolate manufacturing process. Secondly, a hypocholesterolemic drug, eflucimibe, has been processed. A new process using three different steps has allowed a significant improvement in dissolution rate and oral bioavailability

Extrusion de l'Eudragit E100 assistée par du CO 2 supercritique : détermination de la distribution des temps de séjour

National audienceL'extrusion est un procédé largement utilisé industriellement pour la mise en forme de matériaux. Dans ce travail, nous nous intéressons plus particulièrement à l'utilisation du dioxyde de carbone supercritique (CO 2 Sc) comme agent porogène pour la fabrication de mousses polymères par extrusion. Pour cela, une extrudeuse monovis a été modifiée afin de pouvoir injecter du CO 2 Sc dissous au sein de la matière extrudée et ainsi fabriquer des mousses. La présence de CO 2 Sc au sein de la matière modifie entre autres les propriétés rhéologiques du matériau et a donc une influence sur l'écoulement dans l'extrudeuse. Afin de caractériser l'écoulement de la matière au sein de l'extrudeuse, des expériences de traçage ont été réalisées en présence et en absence de CO 2. Cela nous a permis de mettre en évidence l'écart de l'écoulement réel à un écoulement piston ainsi que l'influence de la présence de CO 2 dans l'extrudeuse. Mots-clés : extrusion, Eudragit E100, distribution des temps de séjour, dioxyde de carbone, supercritiqu

Development of an improved falling ball viscometer for high-pressure measurements with supercritical CO₂

International audienceThis study presents the development of an improved technique for viscosity measurements under high pressure. The apparatus is based on the principle of the falling ball viscometer, implemented in a high-pressure autoclave fitted with visualisation windows. The originality here is that the balls fall through a tube open at both ends with a diameter slightly greater than that of the balls, allowing a simplified modelling and numerical simulation. A numerical approach has been used for viscosity determination. Calculations have been made with COMSOL Multiphysics® with the laminar Navier–Stokes model for Newtonian mixtures. It includes the specific hydrodynamic effects without the need for a calibration fluid. However, validation experiments were carried out at atmospheric pressure with dimethylsulfoxide (DMSO) at 298, 308 and 318 K and with cocoa butter at 313 and 353 K, with values of viscosity in the range from 1.4 to 45.4 mPa s. Comparative measurements with literature data have been conducted with cocoa butter saturated with carbon dioxide at 313 and 353 K and for pressures ranging from 0.1 to 25 MPa. At 313 K, viscosity varies from 45.4 mPa s to 3.1 mPa s while at 353 K it varies from 12.4 to 1.9 mPa s. For both isotherms tested, within the range 0–15 MPa, the higher the CO2 dissolution in the cocoa butter, the lower the viscosity. However, this decrease in viscosity is more pronounced at the lowest temperature. Above 15 MPa the CO2 dissolution effect on viscosity becomes insignificant, i.e. within the experimental error, due to a counter effect linked with the high hydrostatic pressure. Furthermore, the limits of use of this method have been determined. This technique is revealed as reliable and can therefore be used with other binary systems

La génération de solides divisés par voie supercritique : principes de base, considérations sur l'état d'avancement des recherches

National audienceOn se propose ici de faire le point sur la génération de solides divisés par voie supercritique : les principes de base des différents types de procédés existants sont donnés. On fait également le point sur l'état d'avancement des connaissances sur ces procédés. L'exemple de leur application dans le domaine pharmaceutique est abordé

Short-term implantation effects of a DCPD-based calcium phosphate cement

International audienceCalcium phosphate cements can be handled in paste form and set in a wet medium after precipitation of calcium phosphate crystals in the implantation site. Depending on the products entering into the chemical reaction leading to the precipitation of calcium phosphates, different phases can be obtained with different mechanical properties, setting times and injectability. We tested a cement composed of a powder, containing-tricalcium phosphate (-TCP) and sodium pyrophosphate mixed with a solution of phosphoric and sulphuric acids. The cement set under a dicalcium phosphate dihydrate (DCPD)-based matrix containing-TCP particles. This was injected with a syringe into a defect drilled in rabbit condyles, the control being an identical defect left empty in the opposite condyle. The condyles were analysed histologically 2, 6 and 18 weeks after implantation. After injection into the bone defect the cement set and formed a porous calcium phosphate structure. Two different calcium phosphate phases with different solubility rates could be identified by scanning electron microscopy (SEM) observation. The less-soluble fragments could be degraded by cell phagocytosis in cell compartments of low pH or integrated in the newly formed bone matrix. The degradation rate of the material was relatively high but compatible with the ingrowth of bone trabeculae within the resorbing material. The ossification process was different from the creeping substitution occurring at the ceramic contact. Bone did not form directly at the cement surface following the differentiation of osteoblasts at the material surface. The trabeculae came to the material surface from the edges of the implantation site. Bone formation in the implantation site was significantly higher than in the control region during the first week of implantation. In conclusion, this material set in situ was well tolerated, inducing a mild foreign-body reaction, which did not impair its replacement by newly formed bone within a few weeks

Développement d'un procédé propre assisté par CO2 supercritique pour la production de particules de polyamide (caractérisation et faisabilité)

Cette thèse vise à la production de poudre de polymère par un procédé continu, en une seule étape et supprimant l'utilisation des solvants organiques en faveur de celle du CO2 supercritique. Avant de développer le procédé, une caractérisation du mélange CO2/polymère a été effectuée. Des mesures de solubilité, de gonflement et de coefficient de diffusion du CO2 ont été réalisées et représentées par différents modèles. De plus, une technique de rhéologie capillaire en ligne a été développée, permettant la mesure de viscosité du polymère, seul ou en mélange, avec le CO2 dans les conditions du procédé. Un montage batch a ensuite permis de tester l'influence des paramètres opératoires sur de faibles quantités. Parallèlement, le procédé continu a été étudié sur une extrudeuse équipée d'outils de mélange du CO2 dans le polymère fondu. L'efficacité et l'homogénéité du mélange ont été étudiées à travers la fabrication de mousses de polymères et la réalisation de distributions de temps de séjour par spectroscopie Raman en ligne. L'ajout d'un dispositif de pulvérisation spécifique a conduit à l'obtention de poudres d'aspect fibreux avec deux populations de tailles.Polymer powders are widely used in industry and are traditionally manufactured by processes using organic solvent or by grinding low molecular weight polymers with a post-polymerization step. This thesis aimss at the generation of polymer powders with a single-step continuous process, based on the use of supercritical CO2, hence without organic solvent. Before developing this process, the characterization of the mixture CO2/polymer was done. Solubility measurements were carried out and fitted with the Sanchez-Lacombe equation of state. Moreover, a capillary rheometry technique was implemented on-line, allowing the measurement of the viscosity of the polymer alone or in mixture with CO2, under process conditions. The modeling of swelling as a function of time led to the evaluation of the diffusion coefficient of CO2 into the polymer. Afterwards, two experimental devices were designed. A batch process with a pressurized autoclave was used to determine the influence of experimental parameters on powder production, with small amounts of material. Formation of small fibrous particles was obtained. In parallel, the continuous process was studied on an extruder adapted to CO2 introduction and equipped with mixing devices. This study, which led to foam manufacture, was used to evaluate efficiency and homogeneity of the mixing. Residence time distributions were determined by Raman spectroscopy on the die in order to evaluate the flowing in the extruder under different conditions. The equipment was also fitted with a specific nozzle allowing co-injection of hot air. Production of fibrous particles with two different size ranges was obtained.TOULOUSE-INP (315552154) / SudocSudocFranceF