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

Abstract : 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.
Complete list of metadatas

Cited literature [1 references]  Display  Hide  Download

https://hal-mines-albi.archives-ouvertes.fr/hal-01730596
Contributor : Jacques Fages <>
Submitted on : Friday, March 16, 2018 - 2:01:56 PM
Last modification on : Thursday, July 19, 2018 - 4:54:01 PM
Long-term archiving on : Tuesday, September 11, 2018 - 3:26:14 AM

File

2007-Sauceau-BookSolubilities-...
Explicit agreement for this submission

Ce document remplace le précédent dépôt car ce dernier ne correspondait pas à l'accord obtenu de l'éditeur.

Identifiers

Collections

Citation

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-01730596v2⟩

Share

Metrics

Record views

143

Files downloads

70