Monotropic systems

A different situation exists if the compound exists as form I and form III. This is referred to as a monotropic system, and here III is unstable relative to I over the whole solid range. In this case, however, the melting point of the unstable polymorph is lower than that of the stable (Tis lower than T ). 

Based on the reversibility of their phase transformation behavior, polymorphs can easily be classified as being either enantiotropic (interchange reversibly with temperature) or monotropic (irreversible phase transformation). Enantiotropic polymorphs are each characterized by phase stability over well-defined temperature ranges. In the monotropic system, one polymorph will be stable at all temperatures, and the other is only metastable. Ostwald formulated the rule of successive reactions, which states that the phase that will crystallize out of a melt will be the state that can be reached with the minimum loss of free... 

Figure 5. shows the solubility curves for a monotropic system of two polymorphs and will be used to discuss methods for controlling the polymorphic form of the product. In this instance the thermodynamically stable and thus least soluble polymorph is Form I. 

Figure 5 Seeding to Control the Polymorphic Form in a Monotropic System...

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 8.40 Free energy vs. temperature diagrams for two polymorphs (forms I and II) showing free energy crossing points (a) enantiotropic system (b) monotropic system.

Fig. 2.6 Pressure vs temperature plots. I/v. and II/v. represent sublimation curves I.v. is the boiling point curve. Broken lines represent regions which are thermodynamically unstable or inaccessible, (a) enantiotropic system (b) monotropic system. The labelling corresponds to earlier figures to indicate that Form I is stable at room temperature which is below the transition point in the enantiotropic case. (From McCrone 1965, with permission.)...

Obtaining the thermodynamically stable form in a monotropic system no transformation can take place to another form, and no precautions need be taken to preserve the stable form or to prevent a transformation. 

Obtaining the thermodynamically metastable form in a monotropic system a kinetically controlled transformation may take place to the undesired thermodynamically stable form. To prevent such a transformation it may be necessary to employ drastic conditions to reduce kinetic effects (e.g. very low temperatures, very dry conditions, storage in the dark, etc.)... 

Enantiotropic systems LT = low-temperature form, HT = high-temperature fortiL Monotropic systems S = stable form, MS = metastable form. 

The thermodynamic activity of each crystalline form, represented by its solubility, may change quite differently as a function of temperature. Monotropic systems are dehned as systems where a single form is always more stable regardless of the temperature. Enantiotropic systems are dehned as systems where the relative stability of the two forms inverts at some transition temperature (Bym et al., 1999). 

Polymorphs and pseudopolymorphs can also be classified as monotropes or enantiotropes, depending upon whether or not one form can transform reversibly to another. In a monotropic system. Form I does transform to Form II, because the transition temperature cannot appear before the melting temperature (Fig. 5,... 

Figure 5 Monotropic system as a function of temperature (x-axis).

Figure 1 Energy-temperature diagrams, (a) For a hypothetical enantiotropic system T and T, melting points of forms I and II 7, transition temperature, (b) For a hypothetical monotropic system 7 and 7n, melting points of forms I and II.

A similar analysis may be used for monotropic systems (Figure 3.4). In this case, the lower melting point 11 polymorph is metastable to the higher melting 1... 

FIGURE 3.4 Schematic DSC traces showing the thermal behavior of monotropic systems under three sets of conditions (a) melting of 1, (b) solid-state transformation of 11 to 1 followed by melting of 1, and (c) melting of 11 followed by recrystallization and then melting of 1. (Based on Giron, D., Thermochim. Acta, 248, 1, 1995.)... 

Fig. 42 Energy-temperature diagrams for a monotropic system (top) and an enantio-tropic system (bottom).

Sometimes only one polymorph is stable at all temperatures below the melting point, with all other polymorphs being therefore unstable. These polymorphs are said to be monotropes, and the system of the two solid phases is said to be monotropic. For a monotropic system... 

Relationship between the Gibbs free energy G and the temperature T for two polymorphs for (a) an enantiotropic system and (b) a monotropic system in which the system is cooled from point X [9]. The arrows indicate the direction of change. (Reproduced with permission of the copyright owner, Elsevier, Amsterdam,... 

The phase diagram of a hypothetical monotropic system is illustrated in Fig. 8. The S1-S2-V triple point (transition point) point is clearly virtual in that fusion of all solid phases takes place before the thermodynamic point of phase stability can be attained. The phase diagram indicates that only one of the polymorphs can be stable at all temperatures up to the melting point, and the other polymorph must... 

Figure 7 Energy/temperature diagrams of polymorphic systems (a) an enantio-tropic system, (b) a monotropic system. (From Ref. 22. Reproduced by permission of Springer, Vienna.)...

Seeding is also recommended for monotropic systems. For the stable polymorph, the temperature after seeding should be held constant for a predetermined time to allow the solution to desupersaturate, after which an appropriate cooling profile (section 7.5.5) should be adopted to maintain a constant controlled supersaturation. If the metastable polymorph is required, and the... 

For enantiotropic thermotropic liquid crystals, the crystallization may occur only from the liquid crystalline phase, provided that the temperature is sufficiently decreased to a range where the crystalline phase is the most stable one. In monotropic systems, the liquid crystalline phase is metastable, and crystallization may occur either from the isotropic melt or from the liquid crystalline... 

---