(Solid+liquid) solubility of organic compounds in organic solvents – Correlation and extrapolation

Abstract

A semi-empirical model is developed for the regression of solid-liquid solubility data with temperature. The model fulfils the required boundary conditions, allowing for robust extrapolation to higher and lower temperatures. The model combines a representation of the solid-state activity which accommodates a temperature-dependent heat capacity difference contribution with a scaled three-parameter Weibull function representing the temperature dependence of the solution activity coefficient at equilibrium. Evaluation of the model is based on previously published experimental calorimetric and solubility data of four organic compounds, fenoxycarb, fenofibrate, risperidone and butyl paraben, in five common organic solvents, methanol, ethyl acetate, acetone, acetonitrile, and toluene. The temperature dependence of the van't Hoff enthalpy of solution and its components is analysed and discussed. Among the four compounds the influence of temperature on the enthalpy of fusion varies from moderate to substantial. Based on the semi-empirical model, a new equation containing three adjustable parameters is proposed for regression and extrapolation of solubility data for cases when only melting data and solubility data is available. The equation is shown to provide good accuracy and robustness when evaluated against the full semiempirical model as well as against commonly used, more simple empirical equations. It is shown how such a model can be used to obtain an estimate of the heat capacity difference for cases where accurate solubility data is available in multiple solvents.2

Thermodynamic Stability Analysis of Tolbutamide Polymorphs and Solubility in Organic Solvents

“…Van't Hoff plots are often used to linearly extrapolate solubility values to higher temperatures, and even for predicting melting points. However, linearity in a van't Hoff plot is not to be expected, [10] and when it is occasionally observed it is the result of a cancelling out of the temperature dependences of the enthalpy of fusion of the pure solid and the solution activity coefficient. [11] The van't Hoff curves of the solubility of FII in all investigated solvents are visibly non-linear.…”

“…The second model is a recently-proposed semi-empirical solubility regression equation, [10] the principle of which is the separation of the temperature dependence of the activity of the pure solid from that of the activity coefficient of the saturated solution. The solubility then becomes: eq s eq eq eq ln ln ln ln ln…”

“…11 obeys thermodynamic boundary conditions at the melting point. [10] . Consequently, the combination of Eq.…”

“…This makes it an appropriate model for correlating solubility data for purposes of extrapolation outside the experimental temperature range. [10] The regression coefficients of Eq. 8 and Eq.…”

Calorimetric Properties and Solubility in Five Pure Organic Solvents of N-Methyl-d-Glucamine (Meglumine)

“…Recently, we proposed a new semi-empirical solubility regression model, suitable both for interpolation and extrapolation to higher temperatures. 6 The basis for our model is the separation of the solventindependent part of the solubility (the activity of the solid, a S , also known as the ideal solubility), from the solvent-dependent part (the activity coefficient in a saturated solution, γeq):…”