Solubilization of Trans-Resveratrol in Some Mono-Solvents and Various Propylene Glycol + Water Mixtures

Abstract

This research deals with the determination of solubility, Hansen solubility parameters, dissolution properties, enthalpy-entropy compensation, and computational modeling of a naturally-derived bioactive compound trans-resveratrol (TRV) in water, methanol, ethanol, n-propanol, n-butanol, propylene glycol (PG), and various PG + water mixtures. The solubility of TRV in six different mono-solvents and various PG + water mixtures was determined at 298.2-318.2 K and 0.1 MPa. The measured experimental solubility values of TRV were regressed using six different computational/theoretical models, including van't Hoff, Apelblat, Buchowski-Ksiazczak λh, Yalkowsly-Roseman, Jouyban-Acree, and van't Hoff-Jouyban-Acree models, with average uncertainties of less than 3.0%. The maxima of TRV solubility in mole fraction was obtained in neat PG (2.62 × 10^-2) at 318.2 K. However, the minima of TRV solubility in the mole fraction was recorded in neat water (3.12 × 10^-6) at 298.2 K. Thermodynamic calculation of TRV dissolution properties suggested an endothermic and entropy-driven dissolution of TRV in all studied mono-solvents and various PG + water mixtures. Solvation behavior evaluation indicated an enthalpy-driven mechanism as the main mechanism for TRV solvation. Based on these data and observations, PG has been chosen as the best mono-solvent for TRV solubilization.

Keywords: Hansen solubility parameters; computational modeling; dissolution properties; solubility; trans-resveratrol.

Figure 1

Molecular structure of trans-resveratrol (TRV).

Figure 2

A graphical comparison of TRV solubility in neat water with reported values at different temperatures; the symbol represents the experimental TRV solubility in neat water; the symbol represents the reported solubility values of TRV in neat water taken from reference [27]; the symbol represents the reported solubility values of TRV in neat water taken from reference [1].

Figure 3

A graphical comparison of TRV solubility in neat ethanol with reported values at different temperatures; the symbol represents the experimental TRV solubility in neat ethanol; the symbol represents the reported solubility values of TRV in neat ethanol taken from reference [27]; the symbol represents the reported solubility values of TRV in neat ethanol taken from reference [1]; the symbol represents the reported solubility values of TRV in neat ethanol taken from reference [2].

Figure 4

A graphical comparison of TRV solubility in (A) neat methanol, (B) neat n-propanol, and (C) neat n-butanol with its reported values at different temperatures; the symbol represents the experimental solubility of TRV in (A) neat methanol, (B) neat n-propanol, and (C) neat n-butanol; the symbol represents the reported solubility values of TRV in (A) neat methanol, (B) neat n-propanol, and (C) neat n-butanol taken from reference [27]; the symbol represents the reported solubility values of TRV in (A) neat methanol, (B) neat n-propanol, and (C) neat n-butanol taken from reference [2].

Figure 5

The effect of the propylene glycol (PG) mass fraction (m) on logarithmic solubility (ln x_e) values of TRV at five different temperatures.

Figure 6

The correlation of ln x_e values of TRV with the modified Apelblat model in six different mono-solvents as a function of 1/T; symbols represent the experimental solubilities of TRV, and solid lines represent the solubilities of TRV calculated using the modified Apelblat model.

Figure 7

The correlation of ln x_e values of TRV with the modified Apelblat model in various PG + water compositions as a function of 1/T; symbols represent the experimental solubilities of TRV, and solid lines represent the solubilities of TRV calculated using the modified Apelblat model.

Figure 8

Δ_solH⁰ vs. Δ_solG⁰ enthalpy–entropy compensation plot for the solubility of TRV in various PG + water compositions at T_hm = 308 K.