Melt Phase Diagrams

Figure 2.1. Examples of melting phase diagrams of binary systems showing complete mutual solubility in the solid and in the liquid states (L liquid field, S solid field). The melting behaviour of the Mo-V, Cs-Rb and Ca-Sr alloys is presented. Notice the different ranges of temperature involved. The melting points of the pure metal components are shown on the corresponding vertical axes. The Cs-Rb is an example of a system showing a minimum in the melting temperature. In the Sr-Ca system complete mutual solid solubility is shown in both the allotropic forms a and (3 of the two metals.

Figure 2.9. Examples of melting phase diagrams of binary systems showing complete mutual solubility in the liquid state and, at high temperature only, in the solid state. By lowering the temperature, however, the continuous solid solution decomposes into two phases. In (d) a schematic representation of NiAu or PtAu type diagrams is shown as formed by two generic components A and B.

Figure 12. Proposed schematic low-coverage melting phase diagram of N2 on graphite according to the tricritical point model. Full lines correspond to the ideal thermodynamic system that is, AT = 0. Dashed curves were obtained with two different temperature smear-ings AT > 0. (Adapted from Fig. 3 of Ref. 276.)...

Less than 1% of racemic species are pseudoracemates, which show typical phase diagrams of continuous solid solutions. Figure 2c shows the three types of melting phase diagrams of pseudoracemates, which comprise ideal solid solutions, solid solutions with positive deviations from ideality, and solid solutions with negative deviations from ideality, respectively [13]. In real systems, the enantiomers and the racemic compound may display a small mutual solubility, even if they show eutectic behavior, which corresponds to terminal solid solutions for which the phase diagrams are shown in Figs. 2d and 2e. 

For chiral drugs, it is usually necessary to apply several techniques to characterize both the enantiomer and the racemic species in order to interpret the origin of the polymorphism among the racemic species. For example, three monotropically related polymorphs of (R5)-nitrendipine were found [29]. Based on the melting phase diagram, IR spectra, and PXRD patterns, the thermodynamically stable form (I) of (R5)-nitrendipine was shown to be a racemic compound, while the other polymorphs, forms II and III, were both found to be conglomerates. Study of one of the pure... 

The phase diagrams in Figure 3.7 consider only SLE. In addition, solid-solid equilibria (e.g. polymorphic phase transitions), liquid-liquid equilibria such as a misdbihty gap in liquid state (hquid-liquid demixing) and also nonequilibrium phenomena (out-of-equilibrium states) can complicate melt phase diagrams and make their measurement more difficult. 

Melt phase diagrams can be determined using different methods of thermal analysis. Here, a substance is subjected to a controlled temperature program and a physical or physicochemical property of this substance is measured as a function of temperature. 

As DSC is the essential method for quantifying SLE for melt phase diagrams, it should be briefly introduced. DSC provides quantitative information about exothermal and endothermal events occurring within the sample as a function of temperature and/or time. It uses the differential principle, that is, measuring the difference of the heat flux between a sample S and a suitable reference R. In an experiment, S and R are subjected to the same programmed temperature profile, while continuously detecting the temperature difference between them. 

Figure 3.11 Melt phase diagram ofthe a-// -epimers. Arrows illustrate cooling of a melt of an 1 1 mixture of the epimers. (Reproduced with permission from Ref [17].)...

Figure 3.29 presents the relation between the binary melt phase diagrams and an isothermal slice of the ternary solubility phase diagrams (introduced in Section 3.1.4). Since the two enantiomers of a chiral system have same melting points and melting enthalpies, their melt phase diagrams are symmetrical to the 1 1 (i.e., racemic) composition. The same applies to the solubility diagrams of the enantiomers as shown in Figure 3.29. Therefore, in general only one haF of the phase diagram has to be measured.

Figure 3.29 The relation of binary melt phase diagrams and ternary solubility phase diagrams of enantiomers. The latter are represented as isothermal slices at an...

J. H. Maas, G. J. Fleer, F. A. M. Leermakers, and M. A. Cohen Stuart, Wetting of a polymer brush by a chemically identical polymer melt phase diagram and film stability, Langmuir, 18, 8871 (2002]. 

Figure 7.1 Melting phase diagram for the potassium fluoride (KF) - aluminium fluoride (AIF3) system...

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