Étude des mécanismes de cristallisation en milieu supercritique - Application à des principes actifs pharmaceutiques (thèse: soutenue au M2P2)
Activités
Cristallisation,
CO2 supercritique,
Simulation,
SAS,
Sulfathiazole, Naphtalène,
GenMol
Publications scientifiques au M2P2
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...
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⟩
Sébastien Clercq, Feral Temelli, Elisabeth Badens. In-Depth Study of Cyclodextrin Complexation with Carotenoids toward the Formation of Enhanced Delivery Systems. Molecular Pharmaceutics, 2021, 18 (4), pp.1720-1729. ⟨10.1021/acs.molpharmaceut.0c01227⟩. ⟨hal-03334353⟩ Plus de détails...
The goal of this study was molecular modeling of cyclodextrin (CD) and carotenoid complex formation. Distinction was made between complexes resulting from interactions between carotenoids and either molecularly dispersed CDs or solid crystalline CDs, considering that both cases can occur depending on the complex formation process pathways. First, the formation of complexes from dispersed CD molecules was investigated considering five different CDs (αCD, βCD, methyl-βCD, hydroxypropyl-βCD, and γCD) and lutein, as a model carotenoid molecule. The interactions involved and the stability of the different complexes formed were evaluated according to the CD size and steric hindrance. Second, the formation of complexes between four different crystalline CDs (βCD with three different water contents and methyl-βCD) and three carotenoid molecules (lutein, lycopene, and β-carotene) was studied. The docking/adsorption of the carotenoid molecules was modeled on the different faces of the CD crystals. The findings highlight that all the CD faces, and thus their growth rates, were equally impacted by the adsorption of the carotenoids. This is due to the fact that all the CD faces are exhibiting similar chemical compositions, the three studied carotenoid molecules are rather chemically similar, and last, the water–carotenoid interactions appear to be weak compared to the CD–carotenoid interactions.
Sébastien Clercq, Feral Temelli, Elisabeth Badens. In-Depth Study of Cyclodextrin Complexation with Carotenoids toward the Formation of Enhanced Delivery Systems. Molecular Pharmaceutics, 2021, 18 (4), pp.1720-1729. ⟨10.1021/acs.molpharmaceut.0c01227⟩. ⟨hal-03334353⟩
Sébastien Clercq, Feral Temelli, Elisabeth Badens. In-Depth Study of Cyclodextrin Complexation with Carotenoids toward the Formation of Enhanced Delivery Systems. Molecular Pharmaceutics, 2021, 18 (4), pp.1720-1729. ⟨10.1021/acs.molpharmaceut.0c01227⟩. ⟨hal-03600451⟩ Plus de détails...
The goal of this study was molecular modeling of cyclodextrin (CD) and carotenoid complex formation. Distinction was made between complexes resulting from interactions between carotenoids and either molecularly dispersed CDs or solid crystalline CDs, considering that both cases can occur depending on the complex formation process pathways. First, the formation of complexes from dispersed CD molecules was investigated considering five different CDs (αCD, βCD, methyl-βCD, hydroxypropyl-βCD, and γCD) and lutein, as a model carotenoid molecule. The interactions involved and the stability of the different complexes formed were evaluated according to the CD size and steric hindrance. Second, the formation of complexes between four different crystalline CDs (βCD with three different water contents and methyl-βCD) and three carotenoid molecules (lutein, lycopene, and β-carotene) was studied. The docking/adsorption of the carotenoid molecules was modeled on the different faces of the CD crystals. The findings highlight that all the CD faces, and thus their growth rates, were equally impacted by the adsorption of the carotenoids. This is due to the fact that all the CD faces are exhibiting similar chemical compositions, the three studied carotenoid molecules are rather chemically similar, and last, the water–carotenoid interactions appear to be weak compared to the CD–carotenoid interactions.
Sébastien Clercq, Feral Temelli, Elisabeth Badens. In-Depth Study of Cyclodextrin Complexation with Carotenoids toward the Formation of Enhanced Delivery Systems. Molecular Pharmaceutics, 2021, 18 (4), pp.1720-1729. ⟨10.1021/acs.molpharmaceut.0c01227⟩. ⟨hal-03600451⟩
Sébastien Clercq, Adil Mouahid, Gérard Pèpe, Elisabeth Badens. Prediction of Crystal–Solvent Interactions in a Supercritical Medium: A Possible Way to Control Crystal Habit at High Supersaturations with Molecular Modeling. Crystal Growth & Design, 2020, 20 (10), pp.6863-6876. ⟨10.1021/acs.cgd.0c00920⟩. ⟨hal-03334336⟩ Plus de détails...
The purpose of this work is to contribute to a better control of the crystallization process which occurs in a supercritical medium, especially during the Supercritical AntiSolvent (SAS) process. It also aims to improve the prediction of crystal habit, thanks to the use of the molecular modeling software GenMol. The first part of the work was devoted to the crystal modeling of the two main forms of sulfathiazole in vacuo, considering Hartman’s attachment energy formalism. The second part considers solvent–crystal interactions throughout adsorption simulations to investigate the effect of growth environments on crystal habits. Lastly, modeling predictions were compared with grown crystals of sulfathiazole, observed after recrystallization with the SAS process from acetonitrile, acetone, tetrahydrofuran and acetic acid solutions. These comparisons demonstrated good predictions of crystal habit taking into consideration the growth environment. Neither carbon dioxide (antisolvent of the SAS process) nor acetonitrile leads to a modification of the isometric, in vacuo predicted habit of both forms. Acetone and tetrahydrofuran adsorb preferentially on some identified faces and lead to flat, leaflike, or tabular crystals. Acetic acid adsorbs on every one of the faces and hinders the phase transition to a more stable form, thus leading to crystals of the least stable, kinetically favored form I. Experimental observations were also rationalized by considering the different possible crystallization pathways, in particular Crystallization by Particle Attachment and Droplet Drying mechanisms occurring in the SAS process. This work confirms that solvent nature is one of the key elements to consider in order to better control the characteristics of particles grown using the SAS process and provides a new method to help to control it.
Sébastien Clercq, Adil Mouahid, Gérard Pèpe, Elisabeth Badens. Prediction of Crystal–Solvent Interactions in a Supercritical Medium: A Possible Way to Control Crystal Habit at High Supersaturations with Molecular Modeling. Crystal Growth & Design, 2020, 20 (10), pp.6863-6876. ⟨10.1021/acs.cgd.0c00920⟩. ⟨hal-03334336⟩
Sébastien Clercq, Adil Mouahid, Pèpe Gérard, Elisabeth Badens. Investigation of crystallization mechanisms for polymorphic and habit control from the Supercritical AntiSolvent process. Journal of Supercritical Fluids, 2018, 141, pp.29-38. ⟨10.1016/j.supflu.2017.11.025⟩. ⟨hal-02113962⟩ Plus de détails...
In this work, the Supercritical AntiSolvent (SAS) process has been used to generate micronized crystals of Sulfathiazole (STZ) from different organic solutions, namely acetone, acetonitrile, tetrahydrofuran and acetic acid. The flow rates of CO2 (2–21 g min−1) and of the organic solution (0.19–6 mL min−1), as well as STZ concentration in the organic solution (20–70% under the saturation), have been varied to identify the conditions leading to powders exhibiting only one polymorphic form. Pressure (10 MPa) and temperature (313 K) have been kept constant. In this paper, thermodynamic and hydrodynamic aspects are discussed so as to rationalize the obtained crystal characteristics and provide a new way to control the SAS process applied to drug pre-formulation. The influence of the organic solvent nature on both the polymorphic form and the habit of generated crystals, has been particularly discussed.
Sébastien Clercq, Adil Mouahid, Pèpe Gérard, Elisabeth Badens. Investigation of crystallization mechanisms for polymorphic and habit control from the Supercritical AntiSolvent process. Journal of Supercritical Fluids, 2018, 141, pp.29-38. ⟨10.1016/j.supflu.2017.11.025⟩. ⟨hal-02113962⟩
