Crystal nucleation in adroplet based microfluidic crystallizer

The study presented in this paper deals with the determination of eflucimibe nucleation rate in a droplet based microfluidic crystallizer. The experimental device allows the storage of up to 2000 monodispersed droplets to get nucleation statistics and crystal growth rates under static conditions. Supersaturation was generated by quenching the droplets down to 273 or 293 K. To determine the nucleation kinetics of eflucimibe, the number of appearing crystals is recorded as a function of time. At low time scale, it was found that eflucimibe in the droplets containing active centers (impurities) crystallizes first and thus yields a rapid initial rate. At higher time scale, once all the droplets containing impurities have crystallized, leaving only the droplets that are free of impurities, the nucleation rate falls allowing the determination of the homogeneous nucleation rate. The crystal–solution interfacial energy found in this system σ=3.12 mJ m−2 is in good agreement with the previously published results. Using the crystalnucleation and the growth rate determined experimentally, simulations were performed using a Monte Carlo method. Even if this method correctly predicts the number of droplets that remains empty during the experiments, it was not possible to predict correctly the number of crystals per drop obtained experimentally. The relationship between the growth and nucleation rates and the resultant number of crystals per drop is likely to be complex and dependent on a number of system parameters. The failure of the model may be attributed either to an overestimation of the crystal growth rate or to an enhancement of the nucleation rate due to the presence of seed crystals

Approches thermodynamiques pour la prédiction de la solubilité de molécules d'intérêt pharmaceutique

La cristallisation est un procédé majeur de l industrie pharmaceutique. Dans la mise au point d un nouveau procédé de cristallisation, l information essentielle est la solubilité de la molécule produite dans le solvant de cristallisation. Cette donnée n est généralement pas connue lors de la phase de développement d un nouveau principe actif. Elle doit donc être déterminée. L objectif de cette thèse est d étudier, et d approfondir, l utilisation de modèles thermodynamiques pour prédire la solubilité de molécules organiques complexes. Pour cela, six molécules sont prises pour référence : l ibuprofène, le paracétamol, les acides salicylique, benzoïque et 4-aminobenzoïque et l anthracène. Les modèles étudiés sont UNIFAC et ses modifications, COSMO-SAC, NRTL-SAC et PC-SAFT. Dans un premier temps, les potentialités de chaque modèle pour prédire la solubilité dans des solvants purs et des mélanges de solvants sont analysées. Dans un second temps, le modèle COSMO-SAC est approfondi et amélioré pour la prédiction des équilibres liquide-solide mettant en jeu des molécules complexes. Enfin, une nouvelle voie de mesure expérimentale de la solubilité dans de très faibles volumes est ouverte par l intermédiaire de l outil microfluidique.Crystallization is a key process of the pharmaceutical industry. When developing a new crystallization process, the most important thing to discover is the final product solubility in a given solvent. However, it is generally unknown at this early step of drug development. The solubility has to be determined. The objective of this work is to study, and deepen, the use of thermodynamic models for solubility predictions of molecules of pharmaceutical interest. To do so, six complex organic molecules have been chosen : ibuprofen, paracetamol, salicylic acid, benzoic acid, 4-aminobenzoic acid and anthracene. The studied models are UNIFAC and its modifications, COSMO-SAC, NRTL-SAC and PC-SAFT. Initially, these models are analysed and used for predicting solubility in pure and mixed solvents. Subsequent work concerns the COSMO-SAC model in more details. It is more particularly improved for solubility predictions. Finally, a road is opened for solubility measurements in low volumes with the use of microfluidics.TOULOUSE-ENSIACET (315552325) / SudocSudocFranceF

Filterability of exopolysaccharides solutions from the red microalga Porphyridium cruentum by tangential filtration on a polymeric membrane

International audienceThe red microalga Porphyridium cruentum is exploited industrially for its exopolysaccharides (EPS) and pigments production. EPS produced by P. cruentum are partially released and dissolved into the surrounding environment, they can be recovered from the culture medium after removing the cells. This paper presents a parametric study of the ultrafiltration of EPS solutions on organic membrane. The EPS solutions were produced in conditions representative of an industrial production. They were filtered at lab-scale on a flat, PES 50 kDa MWCO membrane in a complete recirculation mode of permeate and retentate. Permeate flux-transmembrane pressure (TMP) curves were established up to the limiting flux for the filtration of solutions with various values of concentration in EPS (0.10 to 1.06 kg GlcEq.m), fluid tangential velocity (0.3 to 1.2 m.s) and temperature (20 and 40 °C). The reversible and irreversible parts of fouling were evaluated for each experiment and the critical flux was determined for an intermediate EPS concentration (0.16 kg GlcEq.m). The results showed that EPS solutions had a strong fouling capacity. When filtering the lowest concentrated solution (0.10 kg GlcEq.m) with moderate fouling conditions, the overall fouling resistance was approximately half of the membrane and the share of irreversible/reversible fouling was 88 and 12%. However, the part of reversible fouling becomes predominant when approaching the limiting flux. Permeate fluxes which were obtained allow to estimate that a VRR of approximately 10 could be obtained when concentrating EPS solutions using PES membranes in flat or tubular modules but not in spiral-wound

Performance evaluation of reverse osmosis (RO) pre-treatment technologies for in-land brackish water treatment

Integration of renewable energy with desalination technologies has emerged as an attractive solution to augment fresh water supply sustainably. Fouling and scaling are still considered as limiting factors in membrane desalination processes. For brackish water treatment, pre-treatment of reverse osmosis (RO) feed water is a key step in designing RO plants avoiding membrane fouling. This study aims to compare at pilot scale the rejection efficiency of RO membranes with multiple pre-treatment options at different water recoveries (30, 35, 40, 45 and 50%) and TDS concentrations (3500, 4000, and 4500mg/L). Synthetic brackish water was prepared and performance evaluation were carried out using brackish water reverse osmosis (BWRO) membranes (Filmtec LC-LE-4040 and Hydranautics CPA5-LD-4040) preceded by 5 and 1μm cartridge filters, 0.02μm ultra-filtration (UF) membrane, and forward osmosis (FO) membrane using 0.25M NaCl and MgCl2 as draw solutions (DS). It was revealed that FO membrane with 0.25M MgCl2 used as a draw solution (DS) and Ultra-filtration (UF) membrane followed by Filmtec membrane gave overall 98% rejection but UF facing high fouling potential due to high applied pressure. Use of 5 and 1μm cartridge filter prior to Filmtec membrane also showed effective results with 95% salt rejection

Le controle de la reeducation fonctionnelle respiratoire des exereses partielles par la digraphie et la spirographie associees. (Methode spirodigraphique).

Diss. Toulouse.OPLADEN-RUG0

Le déroulement de l’enquête

Teychene Hervé. Le déroulement de l’enquête . In: Droit et Ville, tome 45, 1998. Colloque : Le commissaire enquêteur est-il majeur ? (Toulouse 30 Mars 1998) pp. 91-95

Maîtrise du polymorphisme dans les procédés de cristallisation de produits d'intérêts pharmaceutiques (application à la cristallisation de l'éflucimibe)

L'éflucimibe est un principe actif cristallisé par refroidissement dont deux formes polymorphes A et B sont susceptibles d'apparaître simultanément. Seule la forme A est souhaitée. L'objectif de cette étude est de comprendre les mécanismes qui gouvernent le polymorphisme. Des techniques de caractérisation des polymorphes ont été mises au point. Les courbes de solubilité des deux formes ont été mesurées expérimentalement et modélisées (UNIQUAC). Les solubilités des deux formes sont très proches. La détermination des cinétiques de nucléation des formes, a permis d'établir un diagramme de prédominance. Ces résultats montrent que la forme A est majoritaire à faible concentration. Les études de cristallisation montrent que si la forme A peut être obtenue, une prise en masse survient, limitant l'extrapolation du procédé. L'étude rhéologique de ces suspensions montre quá partir d'une concentration seuil en particules, elle se structure comme un gelTOULOUSE-ENSIACET (315552325) / SudocSudocFranceF

Profil des nourrissons atteints d allergie aux protéines de lait de vache (étude rétrospective cas-témoins à l hôpital Jean Verdier (Bondy, 93))

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF