Pascale Subra-Paternault

• Ph'D in Analytical Chemistry
• French National Centre for Scientific Research

L'extraction liquide-liquide d'une huile végétale avec de l'éthanol permet d'éliminer principalement lescomposants ayant la plus grande affinité avec l'éthanol, tels que les acides gras libres responsables del'acidité de l'huile, mais aussi certains contaminants comme les phtalates. L'objectif de ce travail estd'étudier l'effet de plusieurs paramèt...

The objective was to evaluate the performance of four hydro-alcoholic solvents to simultaneously extract oil and more polar molecules as phenolics, among others, to produce complex extracts that eventually could self-emulsify after solvent removal. Walnut press-cake was selected as the sourcing material. Extractions were performed as a semi-continu...

L'extraction liquide-liquide d'une huile végétale avec de l'éthanol permet d'éliminer principalement les composants ayant la plus grande affinité avec l'éthanol, tels que les acides gras libres responsables de l'acidité de l'huile, mais aussi certains contaminants comme les phtalates. L'objectif de ce travail est d'étudier l'effet de plusieurs para...

Walnut (Juglans regia L.) press-cake is a residue of oil processing from which the phenolic compounds were extracted using ethanol 60 % by batch and semi-continuous operations, or by ultrasound-assisted maceration in the case of de-oiled cake, with particular attention to the variables time and solid-solvent ratio. For batch extraction, the conditi...

Camelina oil (Coil) contains 50-60% of polyunsaturated fatty acids which are susceptible to oxidation. In this work, addition of phospholipids (0-20 mg/g) was assessed to improve the solubility of quercetin in Coil and enhance its oxidative stability. Results showed that the solubility of quercetin in Coil increased up to 7.7-fold by phospholipid a...

Liquid-liquid extraction of vegetable oil with ethanol predominantly removes the components having the greatest affinity for ethanol, such as free fatty acids responsible for the acidity of oil, but also some contaminants such as phthalates. The aim of this work is to study the effect of several operating parameters on the deacidification process:...

This work aimed the recovery of oil and protein fractions from corn germ (CG) generated as a by-product during flour processing. Several oil extraction techniques were investigated: hexane at room temperature, hexane at 45 °C, supercritical carbon dioxide (Sc-CO2) and Soxhlet with hexane and ethanol. Their influence on oil yield and oil composition...

The extraction of free fatty acids from a walnut oil of acidity 6% was carried out by using either ethanol 96.3% extraction/ decantation stages T 27°C or CO2 + ethanol continuous flow, T 42°C, EtOH from 0 to 14 wt. Results show that FFA cannot be extracted without a co-extraction of oil whatever the process. However the liquid liquid method enables...

Selective extraction of phospholipids (PLs) from camelina press cake and scallop by-products was investigated using Supercritical Fluid Extraction at 45 °C, 25 MPa, with (2–30%) ethanol (EtOH) as co-solvent. A two-step process consisting of a first extraction with CO2 + 7% EtOH to eliminate neutral lipids followed by a second extraction with CO2 +...

Compressed fluids were used in a two-step scheme to extract oil from rapeseed and sunflower spentbleaching earths. The first extraction, performed with CO2at 45◦C, 23 MPa, yielded matrices depleted in neutral lipids (contents of 1% and 3.5% compared to initial 22% and 28%) and of better flowing charac-teristics thanks to the downsizing of particle...

Inactivation of a concentrated threesome of microorganisms (E. coli, S. cerevisiae, L. innocua) in a dietary supplement was investigated using compressed CO2 in batch stirred reactor. Among the operating factors and their range studied through experimental design (20-55 °C, 30-170 bar, duration 30-140 min, depressurization rate 30-120 bar/min), tem...

Camelina, flaxseed, hemp, sesame, and walnut cakes were analyzed for their phospholipid (PL) content and composition using 31P and 1H nuclear magnetic resonance and gas chromatography. The data evidenced variations between the sources in terms of (1) total lipid content and PL concentration, camelina cake being the richest source of PLs, (2) PL com...

Phospholipids (PL) are components of increased value in nutritional applications, especially those rich in polyunsaturated fatty acids (PUFA) such as α‐linolenic acid (ALA, 18:3 n‐3) and linoleic acid (LA, 18:2 n‐6). Currently, the oil processing industry generates by‐products in the form of oilseed and plant cakes that can be valorized for food/fe...

Crystallization assisted by supercritical CO2 has been long ago developed for micronization purposes, but its application to fabricate cocrystals is in its infancy. In this work, the cocrystallization of naproxen and nicotinamide was investigated using CO2 as an antisolvent. In the so-called SAS technique (Supercritical AntiSolvent) a solution of t...

Cocrystallization of naproxen racemic mixture and nicotinamide was investigated in this work, using compressed CO2 as antisolvent. A novel racemic cocrystal structure containing both enantiomers of naproxen linked to nicotinamide has been produced thanks to the CO2 antisolvent batch crystallization process. The structure of the molecular complex an...

In a context of a strong demand for vegetable oils, the development of new “green” processes is essential to provide methods that avoid the use of organic solvents, work at relatively low temperatures and preserve the quality of the final products. The supercritical fluid extraction (SFE) process meets these objectives. In this study, five meals (h...

Micronization, polymorphism, cocrystal formation are well-known strategies to modify characteristics of pharmaceutical ingredients. In this work, recrystallization induced by compressed CO2 as antisolvent was investigated as a new way to produce aminosalicylate (ASA) polymorphs and cocrystals. Three ASA isomers were first recrystallized as single s...

A mathematical model describing the GAS antisolvent process applied to cocrystal formation has been developed with the aim of estimating nucleation and growth parameters that are critical issues in crystallization in general. The estimates are obtained by fitting the particle sizes distribution predicted by the model to experimental data. The inves...

Subcritical extraction (SFE) of dry and ground Golden delicious peels (30 g) was investigated at 25 MPa and 50 °C using CO2 and ethanol (96%) in 75:25 mol ratio. As for conventional ethanol or methanol/acetone/water extraction, nine phenolics were identified in SFE-extracts including the sugar-based phloridzin and quercetin derivatives. Extraction...

In this work, the preparation of hybrid oxo-TiO2 nanoparticles modified by salicylic acid (SA) is reported. The size-selected TiO2 nanoparticles were synthesized in a sal-gel reactor with rapid micromixing of reagents and binding of SA molecules occurs at the nucleation stage. UV-visible absorption, Raman spectroscopy and Light scattering measureme...

The objective was to produce phospholipid-enriched extracts from a new fishery by-product (scallop wastes) using supercritical fluid technology. A two-step fractionation scheme was used to improve the extraction selectivity by first deoiling the dried material by neat CO2 and secondly extracting phospholipids by CO2 plus ethanol. During this step,...

The overall objective of the present work was to modulate the release behavior of drug-impregnated silica particles from almost instantaneous release to a more sustained delivery, prolonged during several hours. Triflusal was chosen as a model drug of the low biodisponibility type. The process is based in the coating with EudragitA (R) RL 100 polym...

In this work, a new setup was designed in order to measure solubility of several solids in a sub or supercritical {CO2-solvent} mixture. The equipment is suitable to operate at temperatures ranging from 293 K to 333K and pressures up to 20 MPa. An analytical method was used, based on a variable-volume cell with sampling of fluid phase for HPLC anal...

Three different powdered hybrid inorganic-organic composites for pharmaceutical use have been successfully obtained using CO2 as an antisolvent in a batch mode process. Naproxen was chosen as the hydrophobic Class II model drug, for which its dissolution rate in water must be enhanced. As excipients, two kind of commercial lipids (G44/14 and G50/13...

In the pharmaceutical sector, a new strategy at nanoscale for modulating the physical and chemical properties of drugs at macroscale is the formation of cocrystals, i.e. multicomponent assemblies of drug (API) and coformer held together by noncovalent interactions. Meanwhile, the need for improved manufacturing technologies is getting more and more...

Cocrystals of naproxen (NPX) and nicotinamide (NCTA) were successfully prepared in acetone using CO2 as antisolvent in the so-called GAS technique (Gaseous Anti Solvent). Infra-red spectroscopy and powder X-ray analysis evidenced the same hydrogen-bond network and stoichiometry than cocrystals produced by cooling crystallization, i.e. 2 NPX for 1 N...

Crystallization induced by compressed CO2 is a process that operates under several MPa of pressure. By rendering on-line measurements very difficult to perform, simulation appears as a suitable tool to better identify the important parameters of the process. A mathematical model is developed in the case of a spray-crystallization process in which a...

This work investigated for the first time a CO2 antisolvent crystallization (SAS) operating in non-isothermal conditions, i.e. injection of a solution warmer than that of the CO2 – in order to impose an additional driving for crystallization when CO2 was not a strong antisolvent. The approach focused on phase equilibria (with a distinctive feature...

The work focused on screening the impact of various excipients and/or procedure in a new method that consists in a CO2-induced precipitation of a drug on a slurry. Naproxen (NPX) is a drug whose bioavailability could be improved by formulation with hydrophilic excipients. The investigated excipients were of various type, size and porosity, i.e. man...

In this work, a two dimensional simulation of segmented micro coflows of CO2 and water in microcapillaries (20 < T (°C) < 50 and 8 < p (MPa) < 16.5) was carried out using a combination of the one-fluid model and the volume of fluid (VOF) method to describe the two-phase flow and a penalty method to account for the wetting property of the capillary...

The context of the study is the Supercritical Antisolvent Process which required as a first step to investigate the disintegration of the injected solvent. In this paper, we focus on the simulation of the jet breakup in biphasic conditions, i.e. when the solution is injected into CO2 under conditions below the mixture critical point where liquid an...

This work proposes for the first time a coprecipitation-on-slurry method using CO2 as antisolvent to prepare formulations of a poorly water-soluble drug (tolbutamide) with micrometric silica (60 and 5 μm) and biopolymers. Mixtures were processed from acetone using the batch gas antisolvent method. Polyethylene glycols and Eudragits were selected as...

This work deals with the simulation of jet disintegration in supercritical conditions. In this validation case, nitrogen at 140 K is injected into a reactor at 298 K in conditions of turbulent flow. The simulation results are confronted with experimental data from literature. The simulation also compares the use of incompressible and compressible m...

In this work we present an experimental set-up used for semi-continuous impregnation per adsorption process of polymers with an organic model component (o-hydroxybenzoic acid – o-HBA) using supercritical CO2 as solvent and impregnating medium. The aim is to study the effect of the supercritical solvent flow-rate, the pressure and the polymer suppor...

Simulations of the growth of a capillary instability and of the breakup of a jet were carried out using a one-fluid model to describe the two-phase flow motion and a VOF approach to capture the interface. The model considered each phase as fictitious sub-domains and accounted implicitly for jump conditions at the interface through a unique set of e...

Recrystallization of theophylline was carried out from an ethanol:methylene chloride solution, using carbon dioxide as antisolvent. The two variants of the technique – bubbling CO2 (GAS) or spraying the solution (SAS) – were investigated in order to explore the effect of specific conditions on physical (particle size distribution) and chemical (cry...

In order to effectively exploit the remarkable properties of fine particles to form hybrid nanostructured composites with applications in the biomedical area, one essential step is their surface functionalization. The overall objective of the present work was to use supercritical carbon dioxide (scCO2) for the design of the surface of inorganic par...

A complete description of the Supercritical Antisolvent Process requires the modeling of several complex phenomena such as heat and mass transfer, hydrodynamic, phase equilibria of ternary mixtures, and nucleation/growth of the specie to be precipitated. As a first step, we focus on the simulation of the heat and mass transfers of binary CO2–solven...

Dans ce travail nous présentons un dispositif expérimental conçu pour l'imprégnation en régime semi-continu de différents types de polymères avec de l'acide salicylique (o-HBA), en milieu CO2 supercritique. L'objectif de ce travail est l'étude sur les paramètres les plus sensibles du procédé : le débit du solvant supercritique, la pression et le ty...

A controlled azacytidine release system based on drug encapsulation with a polymer material has been prepared and characterized. The drug systems were prepared by precipitation from solutions, using supercritical CO2 antisolvent technique operating in a semi-continuous mode. Azacytidine was dissolved in dimethylsulfoxide and poly-lactic acid in met...

Several techniques have been proposed for producing porous structures or scaffolds for tissue engineering but, as yet, with no optimal solution. With regard to this topic, this paper focuses on the preparation of biocompatible nanometric filler-polymer composites organized in a network of fibers. Titanium dioxide (TiO2) or hydroxyapatite (HAP) nano...

In this work the possibility of impregnating P(MMA-EHA-EGDMA) with flurbiprofen using a clean and environmentally friendly technology, namely supercritical fluid technology was evaluated. P(MMA-EHA-EGDMA) has been proposed as a promising matrix to be used for intraocular delivery of anti-inflammatory drugs used in eye surgery and flurbiprofen is a...

A supercritical carbon dioxide (SCCO2) antisolvent technique was used for the precipitation of several biopolymers into fibers organized in a three-dimensional network. The work was first focused on separately processing either a biodegradable (polycaprolactone or polylactic acid) or a non-biodegradable (polymethylmetacrylate) homopolymer. Second,...

The aim of this work is to investigate the crystallization of tolbutamide induced by the addition of compressed carbon dioxide, with a particular focus on the role of the liquor solvent on the product characteristics. Crystals morphology and sizes were documented by microscopy and laser diffraction, respectively; since tolbutamide exists in four po...

Supercritical antisolvent precipitation has been used to produce theophylline particles as pure crystals or as a solid formulation with poly lactic acid (PLA). Experiments were carried out as batch or semi-continuous process and with carbon dioxide (CO2) or trifluoromethane (CHF3) as antisolvent. Both modes led to micronized theophylline, but the s...

Supercritical fluid impregnation was tested to prepare a new ophthalmic drug delivery device. Poly(methylmethacrylate-co-ethylhexylacrylate-co-ethyleneglycoldimethacrylate), P(MMA-EHA-EGDMA) has been proposed by Mariz [M. Mariz, Preparação de uma lente intra-ocular dotada de um sistema de libertação controlada de fármaco, Master Thesis, Universidad...

The use of supercritical fluid and specifically carbon dioxide as carrier to infiltrate various matrices is gaining importance. This study focuses on the impregnation of poly(methyl methacrylate) by a model drug, o-hydroxybenzoic acid (o-HBA), using supercritical carbon dioxide (SCCO2) as carrier and swelling agent, with special emphasis to equilib...

The possibility of preparation of ophthalmic drug delivery systems using compressed anti-solvent technology was evaluated. Eudragit RS 100 and RL 100 were used as drug carriers, acetazolamide was the model drug processed. Compressed anti-solvent experiments were carried out as a semi-continuous or a batch operation from a liquid solution of polymer...

The demand for green technologies is continually increasing due to the growing consciousness of alimentary, environmental and toxicity risks. Supercritical technologies have beneficed from that interest and have therefore received increased attention as propitious media for elaboration of materials in general and formation of particles in particula...

The application of on-line Raman spectroscopy for detecting and monitoring a CO2 antisolvent process (GAS) is explored for the first time. Griseofulvin precipitations were carried out in a batch vessel from an acetone liquor, in which the CO2 was introduced at specific rates. Changes of griseofulvin and acetone concentrations upon addition of CO2 w...

Crystallization induced by supercritical carbon dioxide as non-solvent is gaining importance, but pressurized vessels actually hinder in-situ monitoring of crystallization course. This paper explores for the first time the potentialities of Raman spectroscopy as a tool to determine the composition of the liquid CO2-solvent mixture as CO2 is introdu...

The paper deals with recrystallization of two compounds using CO 2 as anti-solvent. For tolbutamide, comparison between CO 2 -processed and evaporation precipitates clearly indicated the major role of the liquor solvent on the drug form. In acetone, batch and continuous versions produced mostly Form III, with a narrow window for the SAS to add trac...

The recrystallization of a model compound, theophylline, was performed from an ethanol:methylene chloride (EtOH:DCM) solution, using carbon dioxide as antisolvent. Two variants of the antisolvent technique were used : the discontinuous mode in which CO 2 was gradually introduced into the stirred solution, and the semi-continuous mode in which the s...