Isothermal calorimetry sensitivity

Pikal MJ, Dellerman KN. Stability testing of pharmaceuticals by high sensitivity isothermal calorimetry at 25°C cephalosporins in the solid and aqueous solution states. Int J Pharm 1989 50 233-252. 

The kinetics of degradation can be studied using isothermal calorimetry, that is, calorimetry performed at constant temperature. Recently, sensitive thermal conductivity microcalorimeters useful for detecting even small amounts of degradation at room temperature have become available. For example, the slow solid-state degradation of cephalosporins at a rate of approximately 1% per year was successfully measured by microcalorimetry.624... 

H.M. Shirazi, (Quartz Crystal Microbalance/Heat Conduction Calorimetry (QCM/HCC), a new technology capable of isothermal, high sensitivity, mass and heat flow measurements at a solid/gas interface., PhD Thesis, Drexel University, Philadelphia, PA, 2000. 

Pham TN, Watson SA et al (2010) Analysis of amorphous solid dispersions using 2D solid-state NMR and IH T 1 relaxation measurements, vol 7. ACS Publications, New York, pp 1667-1691 Pikal MJ, DeUerman KM (1989) Stability testing of pharmaceuticals by high-sensitivity isothermal calorimetry at 25 C cephalosporins in the solid and aqueous solution states. Int J Pharm 50 233-252... 

With the approach using isothermal thermograms, the different thermograms must be checked for consistency. In certain cases when the peaks are well separated, as for consecutive reactions, they may be treated individually and the heat release rates can be extrapolated separately, and used for the TMRai calculation. The reaction that is active at lower temperature will raise the temperature to a certain level where the second becomes active, and so on. So under adiabatic conditions, one reaction triggers the next as in a chain reaction. In certain cases, in particular for the assessment of stability at storage, it is recommended to use a more sensitive calorimetric method as, for example, Calvet calorimetry or the Thermal Activity Monitor (see Section 4.3), to determine heat release rates at lower temperatures and thus to allow a reliable extrapolation over a large temperature range. Complex reactions can also easily be handled with the iso-conversional method, as mentioned below. 

Immersion calorimetry has much to offer for the characterization of powders and porous solids or for the study of adsorption phenomena. The technique can provide both fundamental and technologically useful information, but for both purposes it is essential to undertake carefully designed experiments. Thus, it is no longer acceptable to make ill-defined heat of immersion measurements. To obtain thermodynamically valid energy, or enthalpy, or immersion data, it is necessary to employ a sensitive microcalorimeter (preferably of the heat-flow isothermal type) and adopt a technique which involves the use of sealed glass sample bulbs and allows ample time (usually one day) for outgassing and the subsequent temperature equilibration. 

Mention should be made here of the recently developed technique of pressure perturbation calorimetry (PPC), which measures the temperature-dependent volume change of a solute or colloidal particle in aqueous solution. PPC can also be used to detect thermotropic phase transitions in lipid model membranes and to characterize the accompanying volume changes and the kinetics of the phase transition. PPC essentially measures the heat change that results from small pressure changes at a constant temperature in a high-sensitivity isothermal calorimeter. For an excellent recent review on PPC as applied to lipid systems, the reader is referred to Heerklotz (19). 

Isothermal titration calorimetry has already reached a state of the art that makes it the method of choice for most solution phase binding studies. The development of the technique does not yet seem to be exhausted, as the sensitivity of the instru-... 

The calorimetric studies of the surface heterogeneity of oxides were initiated half a century ago, and experimental findings as well as their theoretical interpretation have been recently reviewed by Rudzinski and Everett [2]. The last two decades have brought a true Renaissance of adsorption calorimetry. A new generation of fully automatized and computerized microcalorimeters has been developed, far more accurate and easy to manipulate. This was stimulated by the still better recognized fact that calorimetric data are much more sensitive to the nature of an adsorption system than adsorption isotherm for instance. It is related to the fact that calorimetric effects are related to temperature derivatives of appropriate thermodynamic functions, and tempearture appears generally... 

Microcalorimetry is an extremely sensitive technique that determines the heat emitted or adsorbed by a sample in a variety of processes. Microcalorimetry can be used to characterize pharmaceutical solids to obtain heats of solution, heats of crystallization, heats of reaction, heats of dilution, and heats of adsorption. Isothermal microcalorimetry has been used to investigate drug-excipient compatibility [82]. Pikal and co-workers have used isothermal microcalorimetry to investigate the enthalpy of relaxation in amorphous material [83]. Isothermal microcalorimetry is useful in determining even small amounts of amorphous content in a sample [84]. Solution calorimetry has also been used to quantitate the crystallinity of a sample [85]. Other aspects of isothermal microcalorimetry may be obtained from a review by Buckton [86]. 

Differential scanning calorimetry (DSC) is a sensitive method which has enabled changes in biological systems to be examined providing medical researchers with distinct opportunities. Other thermoanalytical techniques such as thermogravimetry (TG) and isothermal titration calorimetry (ITC) are useful in the evaluation of thermal stability and to measure the heat generated in physical and chemical reactions. 

---