Domperidone Solubility in Aqueous Cosolvent Mixtures of N,N-Dimethylformamide, Isopropanol, Dimethyl Sulfoxide, and Ethanol: Thermodynamic Modeling and Preferential Solvation Analysis

Abstract

The determination of solubility of domperidone in aqueous cosolvent mixtures of isopropanol, N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), and ethanol was carried out by a shake-flask method over the temperatures from 293.15 to 333.15 K under local atmospheric pressure p = 101.1 kPa. It may be observed that the domperidone solubility increased and then decreased as the mass fractions of DMF (DMSO, isopropanol, or ethanol) increased. The maximum solubility data was found with the cosolvent composition of 0.8 in mass fraction. The determined solubility values were correlated using the Jouyban–Acree, van’t Hoff–Jouyban–Acree, and Apelblat–Jouyban–Acree models. The attained average relative deviations were smaller than 7.56%. Preferential solvation analysis of domperidone was performed by the inverse Kirkwood–Buff integral method. The preferential solvation parameters (δx 1,3) by the cosolvent showed positive values in the composition regions of 0.20 < x 1 < 0.50 for DMF, 0.24 < x 1 < 0.55 for isopropanol, 0.20 < x 1 < 0.45 for DMSO, and 0.24 < x 1 < 0.61 for ethanol. Domperidone was solvated preferentially by the cosolvents in these regions. We may conjecture that the drug acts as a Lewis acid in the presence of isopropanol (DMF, DMSO, and ethanol) molecules.

Solubility Determination, Computational Methodologies, and Preferential Solvation of 3-Nitro-1,2,4-triazol-5-one in Several Solvent Blends

“…To get the modified van’t Hoff–Jouyban–Acree model (eq ) by modification, we first need to add the van’t Hoff equation, an ideal equation, to eq . ,,,− The numbers D 1 through D 7 are shorthand for the model’s parameters.…”

“…Inverse Kirkwood–Buff integrals, often known as IKBIs, are a method that may be used to depict the local proportions of solvent species that are located close to solute molecules in relation to mole fractions of solutions. This method has seen widespread use in the study of analyzing the preferred solvation behavior of weak electrolytes in systems that contain blended solvents. − ,− ,, The dealing technique makes use of the transfer Gibbs energy of NTO (3) from pure solvents (2), such as water or ethyl acetate, to solutions, in addition to the excess mixing Gibbs energy for solvent blends. Using the most popular solvation parameter, δ x 1,3 , of NTO (3), the analytical findings of this approach are often represented by molecules of solvent (1, alcohol).…”

“…As stated by IKBI theory, eq may be used to represent the δ x 1,3 of NTO (3) by solvent (1) (alcohol) in mixed solvents. − ,− ,, In eq , the variable x 1 represents the bulk mole composition of alcohol (1) in blended solvents without NTO. The variable x 1,3 L represents the local mole fraction of alcohol (1) in the region of NTO in solutions.…”

“…The complete solvation of NTO by alcohol (1) is denoted by the notation δ x 1,3 = 1. The following set of equations might be utilized to ascertain the values for δ x 1,3 . − ,− ,, κ T , expressed on a scale of GPa –1 , signifies the isothermal compressibility of solvent blends. V ̅ 1 , V ̅ 2 , and V ̅ 3 (cm 3 ·mol –1 ), on the other hand, stand for the partial molar volumes of solvent 1 (alcohol), solvent 2 (water or ethyl acetate), and solute 3 (NTO) in the blends that were investigated, respectively.…”

“…V ̅ 1 , V ̅ 2 , and V ̅ 3 (cm 3 ·mol –1 ), on the other hand, stand for the partial molar volumes of solvent 1 (alcohol), solvent 2 (water or ethyl acetate), and solute 3 (NTO) in the blends that were investigated, respectively. Because there is a dearth of information regarding this in the available literature, the molar volume of pure NTO (68.09 cm 3 ·mol –1 calculated through its density) has been utilized for the purposes of this contribution. − ,− ,, As a consequence of this, the molecular radius of NTO, denoted by r 3 , may be determined by employing eq in conjunction with the Avogadro number, N Av . Previous literature has reported the V ̅ 1 , V ̅ 2 , and RT κ T magnitudes for mixtures including alcohol + water and alcohol + ethyl acetate at a temperature of 298.15 K. , Q (in kJ·mol –1 unit) and D (in kJ·mol –1 unit) are the functions that are defined by eqs and with regard to the excess Gibbs free energy of solvent mixtures and the standard transfer Gibbs free energy of NTO from water or ethyl acetate (2) to blended solvents, respectively. To carry out the association of Δ (3,2→1+2) o that is acquired from eq , empirical eq is used, and the parameters of this equation are as follows: A 0 , A 1 , A 2 , t 1 , and t 2 . Because the values of the correlation volume, V cor , are related to the x 1,3 L , an iteration must be performed to discover their values by concurrently examining eqs , , and .…”