International audienceIt is well known that supercritical carbon dioxide (sc-CO 2) is soluble in molten polymers and acts as a plasticizer. The dissolution of sc-CO 2 leads to a decrease in the viscosity of the liquid polymer, the melting point and the glass transition temperature. These properties have been used in several particle generation processes such as PGSS (particles from gas saturated solutions). It is therefore highly likely that extrusion processes would benefit from the use of sc-CO 2 since the rationale of the extrusion processes is to formulate, texture and shape molten polymers by forcing them through a die. Combining these two technologies, extrusion and supercritical fluids, could open up new applications in extrusion. The main advantage of introducing sc-CO 2 in the barrel of an extruder is its function as a plasticizer, which allows the processing of molecules which would otherwise be too fragile to withstand the mechanical stresses and the operating temperatures of a standard extrusion process. In addition, the dissolved CO 2 acts as a foaming agent during expansion through the die. It is therefore possible to control pore generation and growth by controlling the operating conditions. This review focuses on experimental work carried out using continuous extrusion. A continuous process is more economically favourable than batch foaming processes because it is easier to control, has a higher throughput and is very versatile in the properties and shapes of the products obtained. The coupling of extrusion and supercritical CO 2 technologies has already broadened the range of application of extrusion processes. The first applications were developed for the agro-food industry twenty years ago. However, most thermoplastics could potentially be submitted to sc-CO 2-assisted extrusion, opening new challenging opportunities, particularly in the field of pharmaceutical applications. This coupled technology is however still very new and further developments of both experimental and modelling studies will be necessary to gain better theoretical understanding and technical expertise prior to industrial use, especially in the pharmaceutical field

In the pharmaceutical industry, an even greater number of products are in the form of particulate solids. Their formation, formulation and the control of their user properties are still not well understood and mastered. Since the mid-1980s, a new method of powder generation has appeared involving crystallisation with supercritical fluids. Carbon dioxide is the most widely used solvent and its innocuity and ''green'' characteristics make it the best candidate for the pharmaceutical industry. Rapid Expansion of Supercritical Solutions (RESS), Supercritical Anti Solvent (SAS) and Particles from Gas Saturated Solutions (PGSS) are three families of processes which lead to the production of fine and monodisperse powders, including the possibility of controlling crystal polymorphism. For the RESS process, the sudden decompression of the fluid in which a solute has been dissolved is the driving force of nucleation. CO 2 is, however, a rather feeble solvent and this is obviously the main limitation of the development of RESS. In the SAS process, CO 2 acts as a non-solvent for inducing the crystallisation of a solute from an organic solution. The versatility of SAS (there is always a proper solvent-antisolvent couple for the studied solute) ensures future developments for very different types of materials. PGSS uses the fact that it is much easier to dissolve CO 2 in organic solutions (or melted compounds) than the contrary. It presents very promising perspectives of industrial development. After almost 20 years of active research, and more than 10 years of process development, this technology is reaching maturity, and very soon commercial drug produced by these techniques are likely to appear.

Extrusion assisted by supercritical CO 2 (sc-CO 2) is an emerging method for the microcellular foaming of polymer. Instead of batch foaming, which requires formation of single-phase polymer/CO 2 solution in long cycle times, the extrusion assisted by supercritical fluids overcomes this issue by providing rapid mixing and dissolution of CO 2 in the polymer melt. Because the sc-CO 2 is soluble in many molten polymers and acts as a removable plasticizer, its introduction in an extruder will permit a decrease of the processing temperature. This technic allows the use of fragile component like active molecule or starchy and proteinaceous materials. At the end of the extruder, the pressure drop will create instability and phase separation with the creation of porosity. This review is dedicated to the extrusion assisted by sc-CO 2 with different types of biopolymer. Industrial application domains include agro-food, biomedical, pharmaceutical, packaging and many others.

To cite this version:Martial Sauceau, Jean-jacques Letourneau, Dominique Richon, Jacques Fages. Enhanced densitybased models for solid compound solubilities in supercritical carbon dioxide with cosolvents. Fluid AbstractThe ability to correlate and predict the solubility of solids in supercritical fluids is of the utmost importance for the design and the evaluation of supercritical processes. Previously, we have investigated the solubility of a pharmaceutically interesting solid compound in supercritical carbon dioxide, alone or mixed with cosolvents. In this work, these solubility data are correlated through several density-based semi-empirical models. These models have been either modified or extended to be applied to mixtures including a cosolvent. The validity of the resulting correlations is checked by using the solubility data of another pharmaceutical solid, naproxen.

Abstract. Natural fibre reinforced polylactic acid (PLA) foams, as potential green replacements for petroleum-based polymer foams, were investigated. Highly porous (ε > 95%) microcellular PLA foams were manufactured by supercritical CO 2 assisted extrusion process. To overcome the inherently low melt strength of PLA, epoxy-functionalized chain extender was applied, while talc was added to improve its crystallization kinetics. The combined application of chain extender and talc effectively promoted the formation of uniform cell structures. The effect of cellulose and basalt fibre reinforcement on the foamability, morphology, structure and mechanical properties of the PLA foams were investigated as well. The addition of 5 wt% natural fibres promoted the cell nucleation, but caused non-uniform distribution of cell size due to the microholes induced by local fibre-matrix debonding. The compression strength of the manufactured basalt fibre reinforced PLA foams reached 40 kPa.

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The aim of this study is to improve the dissolution properties of a poorly-soluble active substance, Eflucimibe by associating it with gamma-cyclodextrin. To achieve this objective, a new three-step process based on supercritical fluid technology has been proposed. First, Eflucimibe and cyclodextrin are co-crystallized using an anti-solvent process, dimethylsulfoxide being the solvent and supercritical carbon dioxide being the anti-solvent. Second, the co-crystallized powder is held in a static mode under supercritical conditions for several hours. This is the maturing step. Third, in a final stripping step, supercritical CO(2) is flowed through the matured powder to extract the residual solvent. The coupling of the first two steps brings about a significant synergistic effect to improve the dissolution rate of the drug. The nature of the entity obtained at the end of each step is discussed and some suggestions are made as to what happens in these operations. It is shown the co-crystallization ensures a good dispersion of both compounds and is rather insensitive to the operating parameters tested. The maturing step allows some dissolution-recrystallization to occur thus intensifying the intimate contact between the two compounds. Addition of water is necessary to make maturing effective as this is governed by the transfer properties of the medium. The stripping step allows extraction of the residual solvent but also removes some of the Eflucimibe which is the main drawback of this final stage.

In this study, the outcome of operating conditions of extrusion assisted by supercritical CO2 for the manufacture of poly(lactic acid) foams was investigated. It was found that the temperature before and inside the die was the most prominent parameter to tune the foam properties. Foam porosity as high as 96% could be obtained (for die temperature between 109 and 112 °C), representing a total expansion exceeding 30. In this temperature range, low crystallinity (≈6%) was induced giving foams with high radial expansion i.e., large diameters and open porosity. At 112 °C, the CO2 was able to greatly expand the foams, providing 73% of its potential blowing effect. On the other hand, a low die temperature (below a die temperature of 107 °C) induces a significantly higher level of crystallinity resulting in foams with closed‐porosity and a large longitudinal expansion due to higher strength of the polymer melt. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45067.