An investigation of calibration methods for solution calorimetry

Solution calorimetry has been used in a number of varying applications within pharmaceutical research as a technique for the physical characterisation of pharmaceutical materials, such as quantifying small degrees of amorphous content, identifying polymorphs and investigating interactions between drugs and carbohydrates or proteins and carbohydrates. A calibration test procedure is necessary to validate the instrumentation; a few of the suggested calibration reactions are the enthalpies of solution associated with dissolving Tris in 0.1 M HCl or NaCl, KCl or propan-1-ol in water. In addition, there are a number of different methods available to determine enthalpies of solution from the experimental data provided by the calorimeter, for example, the Regnault-Pfaundler's method, a graphical extrapolation based on the Dickinson method, or a manual integration-based method. Thus, the aim of the study was to investigate how each of these methods influences the values for the enthalpy of solution. Experiments were performed according to the method outlined by Hogan and Buckton [Int. J. Pharm. 207 (2000) 57] using KCl (samples of 50, 100 and 200 mg), Tris and sucrose as calibrants. For all three materials the manual integration method was found to be the most consistent with the KCl in water (sample mass of 200 mg) being the most precise. Thus, this method is recommended for the validation of solution calorimeters. (C) 2003 Elsevier B.V. All rights reserved

A comparison of chemical reference materials for solution calorimeters

Solution calorimeters are based on semi-adiabatic or isothermal heat-conduction principles and differ in the way they record data. They also have different measuring sensitivities and require different quantities of solute and solvent. As such, the choice of chemical test substance is not straightforward. Usually the dilution of KCl is recommended; it is possible to purchase a reference sample of KCl that has a certified enthalpy of solution and this standard material is usually used to test semi-adiabatic instruments. Here, we review the suitability of a range of chemical test substances (KCl, sucrose and Tris) for an isothermal heat-conduction solution calorimeter. It was found that KCl was not the best test material because its relatively high enthalpy of solution (Delta(sol)H) necessitated the use of small samples (2 mg), resulting in a relatively large standard deviation (sigma(n-1)) in the values recorded (Delta(sol) H = 17.14 +/- 0.49 kJ mol(-1)); furthermore, KCl data must be corrected to account for the effect of dilution, although the correction was found to be small (0.07 kJ mol(-1)) under the experimental conditions employed here. Sucrose appears to be a much more robust test material for isothermal heat-conduction instruments because its lower enthalpy of solution allows the use of much larger samples (20 mg), which minimises experimental errors. The Delta(sol)H value returned (6.14 +/- 0.08 kJ mol(-1)) is in excellent agreement with the literature. It is also cheap, readily available and requires minimal preparation although its widespread use would require the preparation of a certified reference sample. (c) 2005 Elsevier B.V. All rights reserve