A method to reduce the equilibration time prior to data capture in ampoule-based isothermal microcalorimetric studies

This paper reports a technique for heat conduction isothermal microcalorimeters, which allows, by means of a lowering apparatus, the sample and reference ampoules to be lowered very slowly from the pre-equilibration position to the measuring position. The purpose is to minimize the effect on (total) equilibration time arising from both the pre-equilibration time and the dissipation time (i.e. the time to dissipate the thermal shock which occurs when the vessels are lowered manually). Measurements using 3 ml glass ampoules filled with water, as sample and reference, at 25 and 60 °C, showed that the extent of thermal shock was drastically diminished as the lowering speed decreased, and that the associated heat quantity was reduced to less than 0.2 mJ when lowering occurred over a period of more than 180 s. The dissipation time, the time-period required to dissipate the thermal shock, was also shortened to less than 10 min; the standard manual lowering procedure dissipation time being ca. 25 min. In practice experimental measurements of the imidazole catalysed hydrolysis of triacetin and of the solid state oxidation of ascorbic acid showed that the dissipation time was not shortened when the initial power observed was more than 5 μW, however, it was significantly shortened when the initial power observed was around ≤1 μW. The proposed ampoule lowering procedure could be expected to bring about a saving in the total measurement time for reactions with low initial power, such as those associated with long-term stability studies of relatively stable pharmaceuticals. The described procedure also eliminates operator-induced effects associated with manual lowering of ampoules. In principle the device described also would permit automated loading protocols to be developed.