Measurements and modelling solid solubilities in supercritical phases : application to a pharmaceutical molecule, eflucimibe

Martial Sauceau (1) , Jacques Fages (1)

1 RAPSODEE - Centre de recherche d'Albi en génie des procédés des solides divisés, de l'énergie et de l'environnement

The solubility behaviour of eflucimibe was studied in pure supercritical carbon dioxide at 308 and 318 K between 8 and 30 MPa. The solubility appeared to be an increasing function of both pressure and temperature but remained at very low levels. The effect of two co-solvents, ethanol and DMSO, was then investigated. The solubility was found to be enhanced by both co-solvents, with however a higher increase with DMSO. The co-solvent effect was found to vary nonlin- early with the co-solvent concentration, showing the importance of specific interactions between the co-solvents and the solute in comparison with density effect. These interactions could qualitatively be explained by means of solubil- ity parameters of co-solvents and of solid functional groups. Finally, hydrogen bonds seem to play the most important role in solubility enhancement. To extend these results, modelling appeared to be necessary to provide a tool for prediction of solid solubilities in supercritical mixtures. A study on density- based models, in which effects of density, temperature, and co-solvent compo- sition have been quantified was therefore developed. Solubility data for pharmaceutical solid have been correlated by means of two density – based semi – empirical models: the Chrastil model and the Mendez-Santiago and Teja model. The application of the two correlations to the data in pure CO2 leads to expressions, which can be used for prediction purposes in a large range of pressure-temperature conditions. In addition, they have been extended to be applicable to solvent-cosolvent mixtures considered as pure SCF compounds. This work has confirmed the importance of specific interactions in the co-solvent effect. The representation of all the data with two different co-solvents has been carried out with only one relationship by using a generalized Mendez-Santiago and Teja model, in which effects of density, temperature and co-solvent composition are quantified.

Mots clés: solid solubility; supercritical phases; modelling; eflucimibe

Domaines: Génie des procédés; Pharmacie galénique

Martial Sauceau, Jacques Fages. Measurements and modelling solid solubilities in supercritical phases : application to a pharmaceutical molecule, eflucimibe. Trevor M Letcher. Developments and applications in solubility, The Royal Society of Chemistry, pp.292-304, 2007, 978-0-85404-372-9. ⟨10.1039/9781847557681-00292⟩. ⟨hal-01730596v1⟩