The applications of microcalorimetry in the field of physical pharmacy

Abstract The technique of microcalorimetry is introduced, the instrumental output is shown to relate to thermodynamics, kinetics and the concentration of the reactants (analysis). The detection sensitivity of the instrument is discussed, with particular reference to possible application to isothermal stability testing of solid-state reactions in pharmaceuticals, at ambient conditions: this particular aspect is compared directly to the current practice of use of differential scanning calorimetry (DSC) to screen for excipient incompatibilities. It is necessary to raise the temperature of a reaction significantly to observe a response in a DSC that is detectable at ambient conditions in a microcalorimeter, thus the DSC experiment may give false conclusions if the reaction which occurs at elevated temperatures is not chemically identical to the reaction that proceeds under ambient conditions. Microcalorimetry detects all processes that occur in the reaction cell, this can have advantages in, for example, studies of mechanism, but can cause problems with regard to quantification, the experiment must often be designed to limit investigation to a specific process that is of interest. A selective literature review of applications is presented, which covers stability testing, studies of powder wettability (by immersion and adsorption), crystal properties, dissolution of tablets in artificial foodstuffs and aspects of drug targeting. These examples do not cover the full list of applications, but demonstrate that microcalorimetry can be used to investigate any stage of the development, production and use of a dosage form, e.g. powder properties, excipient compatibility, product stability, tablet dissolution, direct in vitro studies of biological response etc.