UNIFAC group approach

Solubility modelling with activity coefficient methods is an under-utilized tool in the pharmaceutical sector. Within the last few years there have been several new developments that have increased the capabilities of these techniques. The NRTL-SAC model is a flexible new addition to the predictive armory and new software that facilitates local fitting of UNIFAC groups for Pharmaceutical molecules offers an interesting alternative. Quantum chemistry approaches like COSMO-RS [25] and COSMO-SAC [26] may allow realistic ab-initio calculations to be performed, although computational requirements are still restrictive in many corporate environments. Solubility modelling has an important role to play in the efficient development and fundamental understanding of pharmaceutical crystallization processes. The application of these methods to industrially relevant problems, and the development of new... 

UNIFAC Approach Jensen et al. [16] have employed the UNIFAC group contribution approach to develop an estimation method for pure-component vapor pressures. The model developed applies to hydrocarbons, alcohols, ketones, acids, and chloroalkanes of less than 500 molecular mass and in the vapor pressure region between 10 and 2000 mmHg. Burkhard et al. [8] extended this model to chlorinated aromatic compounds such as chlorobenzenes and PCBs. 

There are several theoretical models to estimate the solubility of a solute in a solvent. However, use of dielectric constant is one of the oldest and simplest approach and is very popular with the formulators. Fractional method to estimate the dielectric constant is the simplest approach and is not the most accurate. However, it offers a good starting point for the estimation. In addition, the solubility of a solute is dependent on the dielectric constant of a solvent mixture and not to the particular composition. Other approaches, such as solubility parameter method and UNIFAC group theory contributions are less frequently used by industry formulators. 

Most of the recent theories of liquid solution behavior have been based on well-defined thermodynamic or statistical mechanical assumptions, so that the parameters that appear can be related to the molecular properties of the species in the mixture, and the resulting models have some predictive ability. Although a detailed study of the more fundamental approaches to liquid solution theory is beyond the scope of this book, we consider two examples here the theory of van Laar, which leads to regular solution theory and the UNIFAC group contribution model, which is based on the UNIQUAC model introduced in the previous section. Both regular solution theory and the UNIFAC model are useful for estimating solution behavior in the absence of experimental data. However, neither one is considered sufficiently accurate for the design of a chemical process. 

According to the deviations obtained, it can be concluded that a satisfactory prediction of the solubility of solid phenolic acids in ethyl lactate can be achieved using the equi-fugacity equilibrium condition and UNIFAC group contribution approach to calculate the activity coefficient of the phenolic acid in the liquid ethyl lactate-rich phase. 

The interaction between solvents is important. For example, the development of a successful crystallization process for purification and isolation of an organic compound requires the selection of a suitable solvent or solvent mixture to date, no logical method has been estabhshed for determining the best solvent combination. The process chemist or engineer often employs a trial-and-error procedure to identify an appropriate solvent system, the success of which is dependent on experience and intuition. One approach utilizes a group-contribution method (UNIFAC) to predict a... 

The basis of the UNIFAC approach is the definition of submolecular groups (e.g., CH2, CH3, CH3O, CH2CI, OH) and the fitting of a given molecular property or activity coefficient to a sum of contributions based on the subgroup molecular volume and interaction terms between the groups. 

We recommended two of these methods for general use, estimation from octanol-water partition coefficient and a group contribution method named AQUAFAC. Three other methods are also valuable under certain circumstances, the connectivity, UNIFAC, and sol-vatochromic approaches. 

Another group contribution method that has been applied to the prediction of soil sorption is the UNIquac Functional-group Activity Coefficient (UNIFAC, where UNIQUAC = Universal Quasichemical) approach (Fredenslund et al., 1977). Ames and Grulke (1995) applied the method to a small diverse set of chemicals, with rather poor results. They did not report any correlations, but from their results it can be shown that the correlation of observed and predicted log values using the Bondi method was n = 17, R2 = 0.571, 5 = 0.524, and F = 20.0 eight chemicals were predicted with an error of < 0.5 log units, 7 chemicals were predicted with an error between 0.5 and 1.0 log units, and 2 chemicals were predicted with an error of > 1.0 log units. 

Solubility data of biological compounds taken from literature are considered in this work. Different thermodynamic models based on cubic equations of state and UNIFAC are used in the correlation of experimental data. Interaction parameters are obtained by group contribution approach in order to establish correlations suitable for the prediction of the solid solubility. 

For the analytical equations, there are two methods to compute the vapour-liquid equilibrium for systems. The equation of state method (also known as the direct or phi-phi method) uses an equation of state to describe both the liquid and vapour phase properties, whereas the activity coefficient method (also known as the gamma-phi approach) describes the liquid phase via an activity coefficient model and the vapour phase via an equation of state. Recently, there have also been modified equation of state methods that have an activity coefficient model built into the mixing mles. These methods can be both correlative and predictive. The predictive methods rely on the use of group contribution methods for the activity coefficient models such as UNIFAC and ASOG. Recently, there have also been attempts to develop group contribution methods for the equation of state method, e.g. PRSK. " For a detailed history on the development of equations of state and their applications, as well as activity coefficient models, refer to Wei and Sadus, Sandler and Walas. ... 

The goal of predictive phase equilibrium models is to provide reliable and accurate predictions of the phase behavior of mixtures in the absence of experimental data. For low and moderate pressures, this has been accomplished to a considerable extent by using the group contribution activity coefficient methods, such as the UNIFAC or ASOG models, for the activity coefficient term in eqn. (2.3.8). The combination of such group contribution methods with equations of state is very attractive because it makes the EOS approach completely predictive and the group contribution method... 

With the treatment of gases as individual groups, some binary (or multicomponent) gas-liquid mixtures are reduced to mixtures of only two groups. For example, the carbon dioxide and methanol mixture considered at the conclusion of this section is actually a molecular mixture because both molecules are treated as groups by the UNIFAC approach, Similarly, mixtures of carbon dioxide with benzene or with paraffinic hydrocarbon liquids contain only two groups. The results for such systems are remarkably successful, as will be discussed in this section. The description of mixtures with more than two groups is possible for some of the present models, and the results look promising (Apostolou et al. 1995). 

Perhaps the most important term in Eq. (5.2-3) is the liquid-phase activity coefficient, and mathods for its prediction have been developed in many forms and by many workers. For binery systems die Van Laar [Eq. (1.4-18)]. Wilson [Eq. (1.4-23)]. NRTL (Eq. (1.4-27)], and UNIQUAC [Eq. (1.4-3 )] relationships are useful for predicting liquid-phase nonidealities, but they require some experimental data. When no data are available, and an approximate nonideality correction will suffice, the UNiFAC approach Eq-(1.4-31)], which utilizes functional group contributions, may be used. For special cases Involving regular solutions (no excess entropy of mixing), the Scatchard-Hiidebmod mathod provides liquid-phase activity coefficients based on easily obtained pane-component properties. 

Predictive methods make possible to treat the non-ideality of a liquid mixture without the knowledge of binary interaction parameters fitted from experimental data. Obviously, the predictive should be used only for exploratory purposes. Here we present two approaches. The first one, called the regular solution theory, requires information only about pure components. The second one, UNIFAC, is based on group contributions, and makes use indirectly of experimental data. 

If experimental activity coefficients are unavailable, they can be estimated by, for example, the UNIFAC approach (Fredenslund, Gmehling and Rasmussen, 1977). The UNIFAC model is based on the group contribution concept, calculating the activity coefficients from two parts. The combinato-... 

The simple Flory-Huggins %-function, combined with the solubility parameter approach may be used for a first rough guess about solvent activities of polymer solutions, if no experimental data are available. Nothing more should be expected. This also holds true for any calculations with the UNIFAC-fv or other group-contribution models. For a quantitative representation of solvent activities of polymer solutions, more sophisticated models have to be applied. The choice of a dedicated model, however, may depend, even today, on the nature of the polymer-solvent system and its physical properties (polar or non-polar, association or donor-acceptor interactions, subcritical or supercritical solvents, etc.), on the ranges of temperature, pressure and concentration one is interested in, on the question whether a special solution, special mixture, special application is to be handled or a more universal application is to be foxmd or a software tool is to be developed, on munerical simplicity or, on the other hand, on numerical stability and physically meaningftd roots of the non-linear equation systems to be solved. Finally, it may depend on the experience of the user (and sometimes it still seems to be a matter of taste). 

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