TVIS. Through-Vial Impedance Spectroscopy SMi Lyophilization Europe; July 04-05; Kensington, London, UK

cite as :

Smith G. (2016) TVIS. Through-Vial Impedance Spectroscopy. Podium presentation at SMi Lyophilization Europe; July 04-05; Kensington, London, UK.

The presentation is structured as follows:

1. Basic description of the measurement system hardware

2. Description and Maxwell-Wagner model for the impedance spectrum of the vial containing a liquid formulation

3. Illustration of how the real part impedance spectrum changes towards the end of the ice sublimation phase, and how a measurement at an excitation frequency on the high frequency side of the dielectric relaxation of ice (100 kHz) may be used to track changes in the shape of the ice mass and ultimately determine the end point of the sublimation phase

4. The introduction of a re-heating and re-cooling stage (post freeing) to capture the relationship between the TVIS parameter F_PEAK and the temperature of the ice mass (i.e. to calibrate the TVIS response)

5. The prediction of ice mass temperature during subsequent primary drying from the calibration plot of F_PEAK vs ice mass temperature. This predicted ice mass temperature is given the symbol T(F_PEAK) given that it is derived from the TVIS parameter F_PEAK by a process of calibration.

6. The determination of drying rate from the TVIS parameter C"_PEAK

7. Preliminary attempts at the determination of the vial heat transfer coefficient (K_v)

8. Preliminary studies on freeze-drying conductive liquids: ~4% protein solution and the determination of drying rate

9. The observation of a second relaxation process (on the low frequency side of the ice relaxation peak) and the emergence/dominance of the second relaxation peak as the ice mass is reduced in primary drying. Opportunities now exist for monitoring the secondary drying process when physi-sorbed water is removed form the protein rich unfrozen fraction (i.e. dry layer).