Aqueous solubilities of natural phenolic compounds from different families (hydroxyphenyl, polyphenol,
hydroxybenzoic, and phenylpropenoic) were experimentally obtained. Measurements were performed on tyrosol
and ellagic, protocatechuic, syringic, and o-coumaric acids, at five different temperatures (from 288.2 to
323.2 K), using the standard shake-flask method, followed by compositional analysis using UV spectropho-
tometry. To verify the accuracy of the spectrophotometric method, some data points were measured by
gravimetry, and in general, the values obtained with the two methods are in good agreement (deviations
lower than 11%). To adequately understand the solubilization process, melting properties of the pure phenolics
were obtained by differential scanning calorimetry (DSC), and apparent acid dissociation constants were
measured by potentiometry titration. The aqueous solubilities followed the expected general exponential trend.
The melting temperatures did not follow the same solubility tendency, and for tyrosol and ellagic acid, not
only the size and extent of hydrogen bonding, but also the energy associated with their crystal structures,
determine the solubility. For these binary systems, acid dissociation is not important. Approaches for modeling
the measured data were evaluated. These included an excess Gibbs energy equation, the modified UNIQUAC
model, and the cubic-plus-association (CPA) equation of state. Particularly for the CPA approach, a new
methodology that explicitly takes into account the number and nature of the associating sites and the prediction
of the pure-component parameters from molecular structure is proposed. The results indicate that these are
appropriate tools for representing the water solubilities of these molecules.
In this work, pure solvent solubilities of drugs, such as paracetamol, allopurinol, furosemide and budesonide,
measured in the temperature range between 298.2–315.2K are presented. The solvents under study
were water, ethanol, acetone, ethyl acetate, carbon tetrachloride and n-hexane. Measurements were performed
using the shake-flask method for generating the saturated solutions followed by compositional
analysis by HPLC. Previous literature values on the solubilities of paracetamol were used to assess the
experimental methodology employed in this work. No literature data was found for any of the other
drugs studied in this assay. Melting properties of the pure drugs were also determined by differential
scanning calorimetry (DSC) to provide a broader knowledge about the solubilization process and also for
modeling purposes.
The solubility data as a function of temperaturewere used to determine the thermodynamic properties
of dissolution like, Gibbs energy, enthalpy and entropy. Theoretical work was essentially focused on the
evaluation of theNonrandomTwo-Liquid Segment Activity Coefficient (NRTL-SAC) model, which has been
referred as a simple and practical thermodynamic framework for drug solubility estimation. A satisfactory
agreement was found between experimental and calculated values: the absolute average deviation was
68% for the correlation in the organic solvents and 38% for the prediction in water, where the best results
in prediction could be related to the selected solvents.
Using the analytical gravimetric method the solubility of glycine, DL-alanine, L-isoleucine, L-threonine,
and L-serine in aqueous systems of (NH4)2SO4, at (298.15 and 323.15) K, were measured for salt concentrations
ranging up to 2.0 molal.
In the electrolyte molality range studied the experimental observations showed that ammonium sulfate
is a salting-in agent for most of the amino acids studied. Furthermore, the change of the relative solubility
with electrolyte concentration shows a maximum, which makes the representation of the data by
a simple empirical correlation such as the Setschenow equation difficult. For the development and evaluation
of a robust thermodynamic framework that makes it possible to more profoundly understand
aqueous amino acid solutions with ammonium sulfate additional experimental information is needed.
