Enantiotropism and monotropism

Enantiotropism and monotropism were referred to in Chapter 1. We now provide a thermodynamic basis for these two important descriptors of polymorphic behaviour. 

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Metastable crystalline phases frequently crystallise to a more stable phase in accordance with Ostwald s rule of stages, and the more common types of phase transformation that occur in crystallising and precipitating systems include those between polymorphs and solvates. Transformations can occur in the solid state, particularly at temperatures near the melting point of the crystalline solid, and because of the intervention of a solvent. A stable phase has a lower solubility than a metastable phase, as indicated by the solubility curves in Figures 15.7a and 15.7/ for enantiotropic and monotropic systems respectively and,... 

FIGURE I I Melting point I/temperature K curves for an enantiotropic and monotropic combined system. 

Polymorphism can be classified into two types, enantiotropic and monotropic polymorphism. Each type involves two polymorphic forms or a polymorphic pair, whose interconversion is defined by a characteristic transition temperature. The temperature-dependent solid phase transformation is best understood by referring to the respective energy-temperature diagrams at constant pressure, as depicted in Figure 1 (3). 

The difference between enantiotropic and monotropic forms may be visualized in terms of differences in the temperature-dependent free energy relationship between the respective forms. For enantiotropic polymorphs, there exists a unique temperature (7 0) below the melting point of either form at which the free energy of the two is the same. Consequently, above or below this temperature, either one or the other form will be thermodynamically stable. For monotropic polymorphs,... 

As regards polymorphic transformations in general, two types are distinguished, namely enantiotropic and monotropic [23]. These can be described in terms of the Gibbs free energy G, which has a minimum value for the thermodynamically stable phase of a polymorphic system and larger values for metastable phases and is such that the polymorph with the higher entropy will tend... 

Figure 12. Example of kinetic behaviour of enantiotropic and monotropic transformations. A and B are monotropes to C a- DSC at 10 K/min., A Form A, B Form B, C Form C b - DSC at 5 K/min. of a mixturel of Forms A and C [24]. (With permission from Springer.)...

Enantiotropism and monotropism describe the relationship between polymorphs especially where two polymorphs are being explored. The relationship is enantiotropic when each crystal form has a particular temperature range within which it is stable. A transition point exists where the two forms are equistable and where it is possible for the Pno forms to interconvert. Above the transition point temperature, the/om that is stable at higher temperatures exists exclusively, while below the transition temperature the/orm that is stable at low temperature is stable. It is more usual for the high-temperature/orm to persist outside or beyond its stability range than for the low-temperature form to do so. When one form remains metastable (i.e. with respect to the other form) at all temperatures, then the relationship is considered to be monotropic. The only transition point exists beyond the melt and is therefore unreachable. ... 

Schematic E-T diagrams for enantiotropic and monotropic polymorphs are shown in Figure 8.

Entropy changes are always positive hence, the plots of isobars exhibit a negative slope with increasing temperature as shown in Figure 5a and b for enantiotropic and monotropic systems, respectively. As seen, the transition temperature for the enantiotropic system is below the melting temperature of the individual forms whereas that for monotropic forms is above. Thus, pressure and temperature are the main variables for polymorphic transformations. Since these two variables are the process parameters for an SCF process like the SEDS, such technique facilitates polymorphic screening. 

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