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Citation
Tags
HERO ID
3536967
Reference Type
Journal Article
Title
Solubility of diazepam in water plus tert-butyl alcohol solvent mixtures: Part 1. Experimental data and thermodynamic analysis
Author(s)
Aman-Pommier, F; Degobert, G; Jallut, C
Year
2016
Is Peer Reviewed?
Yes
Journal
Fluid Phase Equilibria
ISSN:
0378-3812
Volume
408
Page Numbers
284-298
DOI
10.1016/j.fluid.2015.10.024
Web of Science Id
WOS:000366784400035
Abstract
The aim of this work is to provide solubility data of a poorly water-soluble drug, diazepam, in water + tert-butyl alcohol solvent mixtures that could be used to train existing cosolvency models and to identify the forces driving the drug solubility variation with the cosolvent content in the solvent mixture. The solubility of diazepam was determined in nine binary solvent mixtures and in both neat solvents at temperatures ranging from 293.15 to 313.15 K under atmospheric pressure. The density of diazepam-free and diazepam-saturated solvent mixtures were also determined as well as the thermophysical properties of original drug crystals and excess solid phases from solid liquid equilibria. The thermodynamic quantities relative to the dissolution process of diazepam under saturation condition were obtained from solubility temperature dependence using the van't Hoff plot. From these data, the changes in thermodynamic quantities of diazepam upon fusion and mixing as well as the excess thermodynamic quantities of the drug in the different saturated solvent compositions over the temperature range investigated were determined using classical thermodynamic approaches. The mole fraction solubility of diazepam increases with the tert-butyl alcohol content in the solvent mixture to reach a maximum in the solvent mixture with a cosolvent mass fraction of 0.90. For every solvent compositions investigated, the transfer of the drug molecules from the pure crystalline solid to the saturated liquid mixtures was found to be endothermic so that the solubility of the drug increases with the temperature. Moreover, for every solvent compositions investigated, enthalpy is the main contributor to the deviation of the systems from ideal behavior, with noticeable exception of neat water. The solubility enhancement of the drug upon increase of the tert-butyl alcohol content in the solvent is then linked to a simultaneous evolution of the partial molar excess entropy and enthalpy of the drug with respect to the solvent composition. (C) 2015 Elsevier B.V. All rights reserved.
Keywords
Diazepam; Tert-butyl alcohol; Solubility; Cosolvent; Thermodynamics
Tags
IRIS
•
tert-Butanol
Excluded/ Not on Topic
Chemical Analysis/Fuel Chemistry
OPPT REs
•
OPPT_N-methylpyrrolidone (NMP)_C. Engineering
Total – title/abstract screening
Off topic
•
OPPT_N-methylpyrrolidone (NMP)_D. Exposure
Total – title/abstract screening
Off topic
•
OPPT_N-methylpyrrolidone (NMP)_E. Fate
Total – title/abstract screening
Off topic
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