Melting point group contribution models

First a database of solute-solvent properties are created in SoluCalc. The database needs the melting point, the enthalpy of fusion and the Hildebrand solubility parameter of the solute (Cimetidine) and the solvents for which solubility data is available. Using the available data, SoluCalc first prepares a list of the most sensitive group interactions and fits sequentially, the solubility data for the minimum set of group interaction parameters that best represent the total data set. For a small set of solvents, the fitted values from SoluCalc are shown in Table 9. It can be noted that while the correlation is very good, the local model is more like a UNIQUAC model than a group contribution model... 

Predictive models for drug-polymer miscibility have been introduced, and they are largely derived from solution thermodynamics. Lattice-based solution models, such as the F-H theory, can be used to assess miscibility in drug-polymer blends, for which the F-H interaction parameter can be considered as a measure of miscibility. In addition, solubility parameter models can be used for this purpose. The methods used to estimate interaction parameters include melting point depression and the determination of solubility parameters using group contribution theory. 

Density is another important physico-chemical property based essentially in the mass of the elements of the compoxmd and their inter-molecular forces. The complexity of this property is lower than the melting point, but in order to have quantitative values, several models were constructed using empirical, group contribution, linear and quantum mechanic methods. The obtained predictions are generally accurate. 

The lattice gas model of Bell et al. [33] neither gave any detailed mechanism of the orientational ordering nor separated the contributions of the headgroup and the acyl chain. Lavis et al. [34] discussed Ref. 33 critically and concluded that the sharp kink point in the isotherm at transition was an artifact of the mean field approximation used. An improved correspondence to experimental data was claimed by the use of the real-space renormalization group method [35]. The same authors returned to the problem [35] and concluded that in addition to the orientation of the molecules, chain melting had to be included in a model which could interpret the phase transitions. 

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