Lyophilization Summit in Vienna May 24-25th 2018
Prof. Geoff Smith gave one of the talks on the first day of the 2nd Annual Lyophilization Summit at the Rainers Hotel, Vienna. In his talk, entitled “Through Vial Impedance Spectroscopy (TVIS): A Novel Process Analytical Technology for
the Development of Pharmaceutical Products and Processes” he explained the use of a dual-electrode TVIS system and its application for determining ice region specific temperatures (, ) and the sublimation rate, from which the heat transfer coefficient () was then calculated Download the slides from the conference:
The dual electrode system comprises two pairs of copper electrodes attached to the outer surface of an Adelphi VC010-20C Type I glass tubing vial, with one large electrode pair enveloping the ice interface region and one smaller electrode pair closer to the base of the vial. The bottom electrode (BE) has height-by-width dimension of 5 × 19 mm and is positioned 3 mm above from the base of the vial whereas the top electrode (TE) has a height-by-dimension of 15 × 19 mm and positioned 3 mm from the top edge of bottom electrode (and therefore 11 mm from the base of the vial) (Fig.1). The dual electrode system is calibrated for temperature against a neighbouring vial which contains two thermocouples (TC1 and TC2) placed at the centre points of the liquid volumes which are bounded by the two electrode pairs. TC2 provides an assessment of the mean ice temperature in the region bounded by the upper electrode pair and TC1 provides an assessment of the mean ice temperature in the region bounded by the bottom electrode pair.
Fig. 1 Method for calibrating the temperature response the dual-electrode-pair TVIS vial using the temperatures determined at equivalent points in the nearest neighbour vial. LEFT : Standard type I glass tubing vial (Adelphi VC010-20 °C of nominal volume 10 mL) with two type-T thermocouples placed at height which are equivalent to the centre points of the upper and lower electrodes; RIGHT: TVIS modified vial with two pairs of copper foil electrodes (only one electrode from each pair is shown here). Ti and Tb are the ice interface temperatures at the sublimation front and at the base of the vial respectively.
During primary drying it is then possible to use the calibrated TVIS response to determine the temperatures at the two reference points and the position of the drying front from which one can then predict the ice interface and ice base temperature (Fig. 2)
Figure 2. A 2 point-temperature determination for extrapolation to the ice interface temperatures of interest. The example shown here is from 2.4 h into primary drying (during the steady state period).
