Differential Scanning Calorimetry DSC

Differential scanning calorimetry  (DSC) is used for examination of all physical processes taking place during heating and cooling of a pharmaceutical compound. Determination of the thermal behaviour is a required part of physical characterisation of a pharmaceutical compound.

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Differential scanning calorimetry is highly relevant in order to:

1. Determine melting point of your compound, for instance as an ID method.
2. Examine the stability of the compound, as transitions or melting at low temperature is not desirable.
3. Evaluate the relative stability of different crystalline forms in order to avoid transitions between forms.
4. Evaluate crystallisation behaviour after heating – which might for instance lead to new polymorphic forms.
5. Compare batches: Differences in energies upon melting might be due to impurities or content of amorphous material and the results might be used for regulatory purposes.

Instrument and measuring principle DSC

Differential Scanning Calorimetry (DSC) measures the temperatures and heat flows associated with transitions in materials as a function of time and temperature in a controlled atmosphere.

A small amount of sample is heated, and if any kind of transition takes place during this process, it will lead to a slight difference between the sample and a reference sample temperature, i.e. diffrential scanning calorimetry measures the amount of energy (heat) absorbed or released by a sample as it is heated, cooled, or held at a constant temperature.

The instrument applied by Particle Analytical is a Mettler DSC 823e Differential Scanning Calorimeter (DSC).

 Technical info Instrument Differential Scanning Calorimeter (DSC) 823e from MettlerToledo Temperatures -65 to 700 °C Heating rate Up to 20 °C/min Sample amount 5-10 mg

Differential scanning calorimetry (DSC) monitors heat effects associated with phase transitions and chemical reactions as a function of temperature and is a very informative method in physical characterisation of a compound. In  Differential Scanning Calorimetry, the difference in heat flow to the sample and a reference at the same temperature, is recorded as a function of temperature. The reference is an inert material such as alumina, or just an empty aluminum pan. The temperature of both the sample and reference are increased at a constant rate. Since the Differential Scanning Calorimeter is at constant pressure, heat flow is equivalent to enthalpy changes:

(dq/dt)p = dH/dt

Here dH/dt is the heat flow measured in mcal sec. The heat flow difference between the sample and the reference is:

ΔdH/dt = (dH/dt)sample – (dH/dt)reference

and can be either positive or negative. In an endothermic process, such as most phase transitions, heat is absorbed and, therefore, heat flow to the sample is higher than that to the reference. Hence ΔdH/dt is positive. Other endothermic processes include helix-coil transitions in DNA, protein denaturation, dehydrations, reduction reactions, and some decomposition reactions. In an exothermic process, such as crystallization, some cross-linking processes, oxidation reactions,and some decomposition reactions, the opposite is true and dH/dt is negative.

• Endothermic:  A transition which absorbs energy.
• Exothermic: A transition which releases energy.

Some examples of uses of Differential Scanning Calorimetry (DSC):

• Glass Transitions: A reversible change of the amorphous region of a polymer from, or to, a viscous or rubbery condition to, or from, a hard and relatively brittle one. The glass transition temperature is a temperature taken to represent the temperature range over which the glass transition takes place. Glass transition temperature is highly relevant for amorphous material as it is a valuable indicator of stability. Thus, DSC can be used in determination of crystallinity of a sample.
• Melting and Boiling Points: The endothermic transition upon heating from a crystalline solid to the liquid state. This process is also called fusion. The enthalpy of melting is the heat energy required for melting, i.e. for breaking down the crystalline lattice. This is calculated by integrating the area of the DSC peak on a time basis. A sharp well defined melting peak corresponds to at well defined crystal structure. Changes in melting temperature and energy gives information about, for instance, content of amorphous material. Thus, the melting endotherm can be used for determination of purity of the sample.
• Crystallization time and temperature: Melting is a one-step process while crystallization involves nucleation and crystal growth. Nucleation will be dependent on cooling rate, whereas the melting point is unaffected. Cooling at different rates might lead to discovery of new polymorphic forms.
• Percent crystallinity/purity: Only crystalline material has a melting endotherm, i.e. a temperature where the lattice breaks down. If a material contains amorphous material – or other impurities, it will lead to a lowering of the melting point + a reduction in the melting enthalpy. Further, content of amophous material will give rise to a glass transition.
• Relative stability of different crystalline forms: Endothermic or exothermic transitions between different crystalline forms (polymorphs) of the same material provide information about their relative stability: From the DSC curve it is possible to reveal whether you have monotropy (one stable form at all temperatures) or anisotropy (a change in relative stability at a given temperature below the melting temperature)
• Changes in heat capacity: Specific Heat Capacity (Cp) is the amount of heat required to raise the temperature of one gram of a particular material one kelvin of temperature. Specific Heat Capacity is due to the molecular motion in a material (units of J/g K).Heat capacity is the amount of heat required to raise the temperature of a material one kelvin of temperature. This is unnormalized specific heat (units of J/K).Specific heat is the specific heat capacity of an analyte compared to the specific heat capacity of a reference material (dimensionless). Crystalline polymers contain more order and thus fewer degrees of molecular motion. Less molecular motion results in lower specific heat capacity. Changes in heat capacity as revealed from a DSC curve gives information about phase changes.