Compatibility studies using isothermal calorimetry

Compatibility testing using isothermal microcalorimetry is used mainly as a screen for drug/excipient chemical interactions and not as a quantitative means of analysis. This is because, at present, it is not possible to obtain information about the quantity of material at the active surface in the solid state (see chemical stability in the solid state section 3.2). 

Within the pharmaceutical industry, bomb calorimetry is used mainly for safety testing of materials. From a calculation of AU an assessment can be made for the explosive force that could be produced if the material was to detonate during rough treatment. During a safety test, the material is shocked under varying conditions of temperature and relative humidity to determine if detonation would take place. During one such study a compound was found to be about 5 times more explosive than nitro-glycerine (AH = 1809 kJ / mol). 

Differences between the heating rate from the drug material and the cooling rate from the container will then allow predictions about the heat build up over time. A thermal run-away reaction can then be avoided. The heat capacity of a material is defined as the energy required to raise 1 g of the material by 1 K. 

In practice the heat capacity of a material can be found by DSC either by reference to known calibrants as sapphire or by the use of modulated methods of thermal analysis [91]. It should be remembered that the best results are for non-reacting systems where the observed calorimetric signal is not complicated by the enthalpy change associated with a chemical reaction. 

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When using calorimetry for compatibility testing, it is imperative to realise the nonspecific nature of the technique. Several physicochemical processes can give rise to a calorimetric response, including wetting, evaporation, dissolution, crystallisation and chemical reaction. Isothermal microcalorimery has been previously employed to study the degradation kinetics of drugs in solution [49] and in the solid state [50]. Recently [51], isothermal... 

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