A substance is said to be polymorphic if it can exist in different crystalline forms, i.e. if the same chemical compound occurs in various modifications with different physical properties. The importance of polymorphism lies in the fact that the physical properties (melting point, color, solubility, refractive index, hardness, conductivity, etc) of a given compound vary from one polymorphic form to the other. The crystalline modifications, however, melt to the same liquid phase.
The polymorphic forms of pharmaceutically active substances are of great practical importance [1]. Since the solubilities and dissolution rates of individual polymorphic forms are very different, resorption and bioavailability in the body also differ [2]. The therapeutic efficiency therefore depends on the modification in question; a metastable form for example can be twice as active as the stable form. Polymorphism is not only important for pharmacological efficiency; it also plays an important role in production, processing and formulation.
The individual crystal modifications that are stable in particular temperature ranges are symbolized by Greek letters (α, β) or Roman numerals (I, II, III). In addition, metastable states (symbolized for example by β’) can also exist whose gradual transformation into stable states may take hours or even years. In accordance with Ostwald’s rule, the less stable modifications are often formed first on crystallizing from the melt. These then rearrange stepwise to the stable forms.
Quite often, it is easier to obtain metastable forms by slowly heating amorphous material (obtained by shock-cooling from the melt) above the glass transition temperature [3]...
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All polymorphic transitions involve a change in enthalpy. This is the reason why DSC is an excellent technique for the investigation of these types of transitions. In the course of a series of such measurements, however, one’s belief in well-defined “melting points” is seriously shaken.
A basic knowledge of the different types of polymorphism is necessary in order to interpret the DSC curves properly. The various examples described in this article should help the newcomer and serve as an introduction to this field.
Polymorphism using DSC | Thermal Analysis Application No. UC82 | Application published in METTLER TOLEDO Thermal Analysis UserCom 8