Enantiotropes metastable phase

Fig. 4.12. DSC thermogram of non-solvated ibuprofen lysinate, illustrating the enantiotropic conversion of the metastable phase to the more stable phase (64°C endotherm) and subsequent melting of the stable form (181°C endotherm).

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 7 Enantiotropic system with metastable phases as a function of temperature (x-axis).

As for monotropic polymorphism, the common L V curve will normally intersect the Si V and -S n-F curves below their intersection (Figure 3) (4). There is no region of stability for the second polymorph (-S ), and the melting point of the metastable An polymorph will invariably be lower than that of the stable form (Ai). Unlike enantiotropic polymorphism, the triple point is always higher than the melting point of the stable 5i phase. Only one of the polymorphs remains stable up to the melting point upon heating, and the other polymorph can exist only as a metastable phase, irrespective of... 

Very complicated phase diagrams can arise when substances can exist in more than two crystalline polymorphs. In certain cases, some of the forms may be enantiotropic to each other, and monotropic to yet others. For instance, of the eight polymorphs of elemental sulfur, only the monoclinic and rhombic modifications exhibit enantiotropy and the possibility of reversible interconversion. All of the other forms are monotropic with respect to the monoclinic and rhombic forms and remain as metastable phases up to the melting point. 

For solids capable of exhibiting polymorphism, in the vicinity of the Sj-Sj-V triple point, the sublimation curve for the metastable phase (Sj-V) will always lie above the sublimation curve for the stable phase (S,-V). It follows that the vapor pressure of a metastable solid phase will always exceed the vapor pressure of the stable phase at a given temperature. This generalization was first deduced by Ostwald, who proved that for a given temperature of a one-component system, the vapor pressure of any metastable phase must exceed that of the stable phase [25]. This behavior was verified for the rhombic and monoclinic polymorphs of elemental sulfur, where it was found that the ordinary transition point of the enantiotropic conversion was 95.5°C [26]. The vapor pressure curve of the rhombic phase was found invariably to exceed that of the monoclinic phase at all temperature values above 95.5°C, while the vapor pressure of the monoclinic phase was higher than that of the rhombic phase below 95.5°C. This behavior provided direct evidence that the rhombic phase was the most stable... 

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... 

It is not uncommon in crystallization processes for the first crystalline phase to make its appearance to be metastable, e.g. a polymorph or hydrate (Ostwald s rule of stages - section 5.7). Some metastable phases rapidly transform to a more stable phase while others can exhibit apparent stability for an exceptionally long time. Some transformations are reversible (enantiotropic) while others are irreversible (monotropic), as explained in sections 1.8 and 4.2.1. In some cases, the metastable phase may have more desirable properties than the stable phase, e.g., a metastable pharmaceutical product may be more pharmacologically active than the stable form. If the required metastable form is first to crystallize, it is important to isolate and dry it quickly to prevent it transforming to the stable form. Once in the dry condition a metastable form can often remain unchanged indefinitely. If the stable polymorph is required, it is essential to create conditions and allow sufficient time in the crystallizer for total transformation to the more stable phase to be ensured. 

In Figure 6.43b, form II is stable at temperatures below the transition temperature T and form I is stable above T. At the transition temperature both forms have the same solubility and reversible transformation between these two enantiotropic forms I and II can be effected by temperature manipulation. Figure 6.43c, however, depicts the intervention of metastable phases (the broken line extensions to the two solubility curves) which bear evidence of the importance of kinetic factors which for a time may override thermodynamic considerations. For example, if a solution of composition and temperature represented by point A (supersaturated with respect to both I and II) is allowed to crystallize it would not be unusual if the metastable form I crystallized out first even though the temperature would suggest that form II is the stable form. This would simply be an example of Ostwald s rule (section 5.7) being followed. This behaviour would occur, for example, if form II had the faster nucleation and/or crystal growth rates. However, if the crystals of form I were kept in contact with the mother liquor, transformation could occur as the more soluble form I crystals dissolve and the less soluble form II crystals nucleate and grow. 

Figure 1.2 illustrates a pure compoimd which exists in both monotropic and enantiotropic phases. Points Si, S2, S3, represent equilibria between stable phases. Point mi represents a metastable equilibrium between two metastable phases. Point m2 represents the melting point of metastable phase crtn, . It is always less than the melting point of the stable phase at this temperature. The trarrsitiorr, ts, is a monotropic trarrsition. Superficially such a trarrsition rrray appear to mimic an eqrrilibrirrm trarrsitiorr. However if the experiment is repeated, the trarrsition terrrperature is not likely to be reproducible. Furthermore the reverse trarrsitiorr, from the stable to the metastable form, carmotbe rrrade to occur. 

Monotropic crystal phases are iderrtified by the symbols, cr,I, cr,n,. .. where cr,I is the phase that can be placed in eqrriUbrirrm with the liqttid, and cr,II, cr,in, are phases that are stable at successively lower temperatures. A metastable crystal above the melting point is said to be superheated. This corrdition is seldom attained in practice. Enantiotropic crystal phases ate iderrtified by the syrrrbol, am, or by crrrr, , crm,II, and so on, if there is mote thm one such phase. The point at which the Gibbs energy of two metastable states crosses represents a constrained equilibrirrm between the phases. 

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... 

On heating from a crystalline phase, DOBAMBC melts to form a SmC phase, which exists as the thermodynamic minimum structure between 76 and 95°C. At 95°C a thermotropic transition to the SmA phase occurs. Finally, the system clears to the isotropic liquid phase at 117°C. On cooling, the SmC phase supercools into the temperature range where the crystalline solid is more stable (a common occurrence). In fact, at 63°C a new smectic phase (the SmF) appears. This phase is metastable with respect to the crystalline solid such phases are termed monotropic, while thermodynamically stable phases are termed enantiotropic. The kinetic stability of monotropic LC phases is dependent upon purity of the sample and other conditions such as the cooling rate. However, the appearance of monotropic phases is typically reproducible and is often reported in the phase sequence on cooling. It is assumed that phases appearing on heating a sample are enantiotropic. 

Another interesting phenomenon found by Stevens et al. is the monotropic mesophase formed by the dimer and trimer of the polymer with m = 6. The dimer has a monotropic nematic phase, the trimer has a monotropic smectic phase. These metastable monotropic phases become stable enantiotropic phases with the increase of n by 1. At about the same time, Blumstein et al. (1984) found the low mass model compound of a main-chain type liquid crystalline polymer was monotropic while the mesophase of the polymer was enantiotropic. 

In most cases, the observed mesophases are found on both heating and cooling a material, so sequence 1 in Scheme 2 is fully reversible such mesophases are termed enantiotropic. However, in some cases a particular mesophase may only appear on cooling a material and is therefore metastable (sequence 2, Scheme 2) such phases are termed monotropic. ... 

The melting behavior of an enantiotropic system is often interesting to observe. If one begins with the polymorph that is less stable at room temperature and heats the solid up to its melting point, the S2-L melting phase transformation is first observed. As the temperature is raised further, the melt is observed to resolidify because the liquid is metastable with respect to the most stable polymorph, Sj. Continued heating will then result in the Sj-L phase transformation. If one allows... 

One of the best known examples of suspended transformation is found with the polymorphs formed by quartz [23]. The three principal polymorphic forms are quartz, tridymite, and cristobalite, which are enantiotropically related to each other. The ordinary transition point for the quartz/tridymite transition is 870°C, while the ordinary transition point for the tridymite/cristobalite transition is 1470°C. The melting point of cristobalite is at 1705°C, which exceeds all of the solid phase transition points. However, the phase transformations of these forms are extremely sluggish, and consequently each mineral form can be found in nature existing in a metastable form. 

In monotropy, one polymorph is always more stable than the other at all temperatures below their melting points (Fig. 7b). This definition is based on the assumption that the pressure remains eonstant. An alternative definition is that, if the pressure temperature phase diagram does not allow a polymorph to be in equilibrium with its vapor phase below the critical point, it is the unstable monotrope, otherwise it is an enantiotrope. This definition recognizes that some monotropes may be thermodynamically stable at elevated pressures and temperatures, e.g., diamond, which is the metastable polymorph of carbon under ambient conditions. 

One example of such metastable enantiotropic behavior is provided by a side chain polysiloxane with the following transitions recorded on heating from the glassy state G 5 S 54 N 1121 [5]. However, a crystal which melts above 54" C (the S-N transition) develops upon annealing the mesophase above Tg, and displaces the smectic phase which becomes monotropic. 

The mesophase state of liquid crystals is normally opaque due to relatively large sizes of ordered domains. Its transition point to the isotropic melt state is called the clear point T,. The DSC scanning curves of liquid crystals can exhibit either enantiotropic or monotropic phenomena. For the thermodynamically stable mesophases of liquid crystals, they occur between the melt and the crystal states during both cooling and heating processes, as illustrated in Fig. 10.5. When both the cooling and heating curves show two symmetric consecutive phase transitions, it is known as the enantiotropic phenomenon. In contrast, for the metastable mesophase... 

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... 

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