Process Understanding in Freeze-Drying Cycle Development: Applications for Through-Vial Impedance Spectroscopy (TVIS) in Mini-pilot Studies

Smith, Geoff; Arshad, Muhammad Sohail; Polygalov, E.; Ermolina, I.; McCoy, Timothy R.; Matejtschuk, Paul

doi:10.1007/s12247-016-9266-5

Cited by 12 publications

(8 citation statements)

References 44 publications

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“…2). We have shown in a previous article [23] that the parameter is sensitive to the average temperature of the ice in the region bounded by the electrodes whereas the parameter ″ , whilst it also has a smaller dependency on temperature, is largely sensitive to the height of the ice cylinder in the region bounded by the electrodes. We also recognize here that the relationship between the magnitude of ″ and the height of the ice layer is only linear if there is intimate contact between the ice and the inside wall of the glass vial (i.e.…”

Section: Measurement Principlesmentioning

confidence: 91%

“…the opposition to current flow when an alternating voltage is applied to the vial, using a pair of electrodes which are attached to the external surface of the glass wall (hence the term "through-vial"). With a through vial impedance measurement it is the changes in the electrical properties of the composite object (comprising the product and the glass wall) that reflect the physical condition of the product during the freeze drying process [23].…”

Section: Through-vial Impedance Spectroscopy (Tvis)mentioning

confidence: 99%

See 1 more Smart Citation

The application of dual-electrode through vial impedance spectroscopy for the determination of ice interface temperatures, primary drying rate and vial heat transfer coefficient in lyophilization process development

Smith

Jeeraruangrattana

Ermolina

2018

European Journal of Pharmaceutics and Biopharmaceutics

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Section: Measurement Principlesmentioning

confidence: 91%

Section: Through-vial Impedance Spectroscopy (Tvis)mentioning

confidence: 99%

The application of dual-electrode through vial impedance spectroscopy for the determination of ice interface temperatures, primary drying rate and vial heat transfer coefficient in lyophilization process development

Smith

Jeeraruangrattana

Ermolina

2018

European Journal of Pharmaceutics and Biopharmaceutics

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“…It has been shown that TVIS measures the average product temperature at the center point of the volume of material bounded by the electrodes [1]. In other words, at a height which is equivalent to the half of the sample height bounded by electrodes; the point that we shall now call the TVIS temperature sensing node or simply the TVIS node (See Figure 1).…”

Section: Vial Filling and Loading The Freeze Dryermentioning

confidence: 99%

“…Consequently, the rate of ice loss could be determined by the rate of change of the measured capacitance, thereby providing an opportunity for monitoring the primary drying process. Smith et al [1] descibed the basic methodology for the determination of sublimation rate by using the magnitude of dielectric loss process associated with the ice content in the vial ( ″ ).…”

Section: Estimation Of the Residual Ice Massmentioning

confidence: 99%

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Determination of ice interface temperature, sublimation rate and the dried product resistance, and its application in the assessment of microcollapse using through-vial impedance spectroscopy

Jeeraruangrattana

Smith

Polygalov

et al. 2020

European Journal of Pharmaceutics and Biopharmaceutics

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Through-vial impedance spectroscopy (TVIS) is a new approach for characterizing product attributes during freeze-drying process development. In this study, a pair of copper foil electrodes was attached to the external surface of a Type I glass tubing vial, of nominal capacity 10 mL and containing 3.5 g of an aqueous solution of 5% w/v lactose, and the impedance spectrum of the vial and contents recorded during a lyophilization cycle. The cycle included a temperature ramp in the primary drying stage in order to induce a collapse event in the dry layer. Using the peak in the dielectric loss spectrum, associated with the dielectric relaxation of ice, methods were developed to predict the sublimation rate and the ice interface temperature at the sublimation front, from which the dry layer resistance was then calculated. A four-fold increase in sublimation rate and a reduction in the dry layer resistance was observed once the the ice interface temperature reached −33 °C, which coincides with the onset of the glass transition (as determined by DSC) and the time point at which micro-collapse occurred (as evidenced by SEM images at the end of the cycle). This work suggests a prospective application of impedance measurements in driving process efficiencies by operating the dryer at the highest achievable temperature (i.e. the collapse temperature) whilst avoiding macro-collapse.

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Through Vial Impedance Spectroscopy (TVIS): A Novel Approach to Process Understanding for Freeze-Drying Cycle Development

Smith

Polygalov

2018

Methods in Pharmacology and Toxicology

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Through vial impedance spectroscopy (TVIS) provides a new process analytical technology for monitoring a development scale lyophilization process, which exploits the changes in the bulk electrical properties that occur on freezing and subsequent drying of a drug solution. Unlike the majority of uses of impedance spectroscopy, for freeze-drying process development, the electrodes do not contact the product but are attached to the outside of the glass vial which is used to contain the product to provide a non-sample-invasive monitoring technology. Impedance spectra (in frequency range 10 Hz to 1 MHz) are generated throughout the drying cycle by a specially designed impedance spectrometer based on a 1 GΩ trans-impedance amplifier and then displayed in terms of complex capacitance. Typical capacitance spectra have one or two peaks in the imaginary capacitance (i.e. the dielectric loss) and the same number of steps in the real part capacitance (i.e. the dielectric permittivity). This chapter explores the underlying mechanisms that are responsible for these dielectric processes, i.e. the Maxwell-Wagner (space charge) polarization of the glass wall of the vial through the contents of the vial when in the liquid state, and the dielectric relaxation of ice when in the frozen state. In future work, it will be demonstrated how to measure product temperature and drying rates within single vials and multiple (clusters) of vials, from which other critical process parameters, such as heat transfer coefficient and dry layer resistance may be determined.

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Process Understanding in Freeze-Drying Cycle Development: Applications for Through-Vial Impedance Spectroscopy (TVIS) in Mini-pilot Studies

Cited by 12 publications

References 44 publications

The application of dual-electrode through vial impedance spectroscopy for the determination of ice interface temperatures, primary drying rate and vial heat transfer coefficient in lyophilization process development

The application of dual-electrode through vial impedance spectroscopy for the determination of ice interface temperatures, primary drying rate and vial heat transfer coefficient in lyophilization process development

Determination of ice interface temperature, sublimation rate and the dried product resistance, and its application in the assessment of microcollapse using through-vial impedance spectroscopy

Through Vial Impedance Spectroscopy (TVIS): A Novel Approach to Process Understanding for Freeze-Drying Cycle Development

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