Determination of solubility profiles of eflucimibe polymorphs: experimental and modeling.
This work presents the determination of the phase diagram of two polymorphs of Eflucimibe in pure solvents and solvent mixtures at different temperatures. Solid phase changes were analysed by Differential Scanning Calorimetry. Solubility measurements show that the solubility of the two forms are very similar. Experimental data obtained in ethanol, reported in a Van t'Hoff plot, exhibit a transition temperature around 265 K. A single maximum is observed when solubility is plotted against the solubility parameters of solvents or solvent mixture and it is not related to a solid phase change. This phenomenon, known as a positive synergetic effect, has been explained in term of evolution of solute-solvents polar interactions. Several thermodynamics models (UNIFAC, UNIQUAC, Wilson, Scatchard Hildebrand ... ) were tested in order to predict the Liquid-Solid Equilibrium for this system. The semi empirical model UNIQUAC gives the best fit. The results obtained are in good agreement with the experimental data (mean deviation lower than 5%) and the solubility maximum found experimentally for each polymorph is also well described.
Laboratoire de Génie Chimique, UMR CNRS 5503, 31106 Toulouse, France. Sebastien.Teychene@ensiacet.fr
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S
Teychene
J M
JM
Autret
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B
Biscans
D000813:Anilides / Q000737:chemistry*; D000924:Anticholesteremic Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D000431:Ethanol / Q000737:chemistry; D006536:Heptanes / Q000737:chemistry; D007700:Kinetics; D008956:Models, Chemical; D044367:Phase Transition; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics; D013818:Thermogravimetry; D044366:Transition Temperature
D000813:Anilides; D000924:Anticholesteremic Agents; D006536:Heptanes; D012997:Solvents; C418062:eflucimibe; D000431:Ethanol; C028618:n-heptane