Solubility Measurement and Thermodynamic Properties of Levetiracetam in Pure and Mixed Solvents

Abstract

In this work, the solid–liquid equilibrium for levetiracetam in 10 neat solvents (methanol, ethanol, n-propanol, isopropanol, acetone, acetonitrile, ethyl acetate, 1,4-dioxane, toluene, and cyclohexane) and binary liquid mixtures (ethanol + ethyl acetate) was measured by using a static gravimetric method at temperatures T = 283.15–323.15 K under pressure of 101.2 kPa. In general, the equilibrium solubility was highest in methanol and lowest in cyclohexane. The modified Apelblat equation, λh equation, Wilson model, and NRTL model were used to correlate the solubility data in monosolvents; and the Jouyban–Acree model, van’t Hoff–Jouyban–Acree model, and Apelblat–Jouyban–Acree model were used to correlate the experiment data in the binary solvent mixtures. Compared with the results of the above models, the calculated solubility provided good results with the experimental data. Consequently, for the monosolvents, the values of root-mean-square deviation and relative average deviation were not exceeding 9.91 × 10–4 and 2.50%, respectively; and for the binary solvent mixtures, 2.75 × 10–4 and 0.80%. Furthermore, the thermodynamic properties of levetiracetam in monosolvents were calculated. From the analysis results, the dissolution process of levetiracetam was an endothermic, spontaneous, and entropy driven process. It is crucially important to understand the solubility and thermodynamic properties of levetiracetam in drug development. In particular, purification, recrystallization, and formulation development of levetiracetam in industry were effected by its solubility values.

Thermodynamic Modeling and Solubility Study of Satranidazole in Different Monosolvents at Different Temperatures

“…in which the coefficients A, B, and C are adjustable model parameters of the Apelblat model. 69 These coefficients of eq 7 were calculated by multivariate regression analysis of experimental solubilities values of SAT listed in Table 2. To correlate X exp values of SAT with X Apl values, the RD and RMSD values were calculated again as reported previously.…”

“…The Apelblat model which was deduced from the Clausius–Clapeyron equation has been widely used in the correlation of solid–liquid equilibrium data. The Apelblat solubility/correlated solubility ( X Apl ) of SAT was calculated using eq : , in which the coefficients A , B , and C are adjustable model parameters of the Apelblat model . These coefficients of eq were calculated by multivariate regression analysis of experimental solubilities values of SAT listed in Table .…”

Separation of Etiracetam Enantiomers Using Enantiospecific Cocrystallization with 2-Chloromandelic Acid

“…To analyze the enantiomeric excess and yield of the resolved enantiomer ( S -ETI), 1 mg of the cocrystal was stirred for 1 h in 150 μL of diethyl ether, which is an appropriate amount of solvent to dissolve most of the S -2CLMA from the cocrystal while obtaining a good yield of S -ETI ( Table S2 ). Diethyl ether was chosen as the solvent for this process since the solubility of S -ETI in this solvent is very low (less than 0.007 g/g of diethyl ether 21 ) compared to the solubility of S -2CLMA (0.369 g/g of diethyl ether 22 ), which makes it suitable for separating the components of the cocrystal. The solubilities of the components in other solvents that were considered are shown in the Supporting Information, Table S3 .…”

Significant Increase in the Solubility of Celecoxib in Presence of Some Deep Eutectic Solvents as Novel Sustainable Solvents and the Thermodynamic Analysis of These Systems

“…(1):where M i and w i denote the molar mass and mass fractions of i component in the saturated solution, respectively. [25][26][27][28]…”

“…The Jouyban-Acree model, as a precise mathematical model can be used to correlate the solubility with respect to temperature and co-solvent composition. 30,31 Its basic form to calculate the solubility of a solute in a binary solvent mixture is: 32 where X m is the mole fraction solubility of the solute in solvent mixture, w 1 and w 2 the weight fractions of solvents 1 and 2 in the absence of the solute, X 1 and X 2 the mole fraction solubilities in neat solvents 1 and 2, respectively, and J i the solvent-solvent and solute-solvent interaction parameters for each binary solvent system. Two data points of solubilities in mono-solvent systems at every temperature should have measured in order to obtain the model parameters.…”