LyoDEA: In-process sensing technology for control of the freeze-drying cycle

LyoDEA™ is a technology that allows in-line measurement of the freeze drying process using impedance analysis of a single vial. Put simply it measures electrical capacitance changes over a range of frequencies as the freeze drying process progresses through its’ key stages; freezing, annealing & sublimation (primary drying). The changes in ice structure during the freezing & annealing stages are critical to the final product quality so it is important that these can be monitored and controlled. LyoDEA facilitates the characterization of structural changes in-line as part of product development. As such it has the potential to shorten development time and produce a more efficient production process,thus saving energy.
The LyoDEA™system measures a “pseudo-relaxation” process associated with the interfacial polarization of the glass wall of the freeze-drying vial through the resistance of the sample. The model represented by the equivalent circuit (below) describes the behaviour of a sample in a freeze drying vial in a course of freeze drying cycle,
Where,C0is the capacitance formed by the electrodes and glass walls of a vial, C1 is the capacitance of the internal volume of a vial and R1 is the electrical resistance of a sample.
The measured changes in electrical capacitance are very small. The initial challenge was to produce equipment sensitive enough to detect these changes beyond the normal fluctuations from the instrument, i.e. to increase the signal to noise ratio. The second challenge is to relate the changes in capacitance to the actual physical changes in the process. We are now seeing a correlation between the signal recorded & physical changes
• Z-view fitting of the LyoDEA spectra provides valuable information relating to eutectic, glass transition and early primary drying.
• Peak data effectively records and phase transition or temperature changes during freezing annealing.
• T slice data from lactose and sucrose based formulations taken at specific frequency (1 kHz) satisfactorily described the end of primary drying in agreement with the thermocouple response.
The project is now in its’ fourth year. There are three LyoDEA™ systems running so data is being constantly generated & analysed which is leading to a greater understanding of the data, what it is showing us and to improvement’s to the LyoDEA™ system.
This project is the result of the collaboration of four partners each with their own specific expertise. Astra Zenecarepresents a technology end user;using LyoDEA™tofocuson the development of the freeze dried products ?ocesses. De Montfort University have developed the initial dielectric theory & continue to produce and analyse data.AmetekAdvanced Measurement Technology is an OEM of signal processing hardware & GEA Pharma Systems are an OEM of freeze dryers and are the project lead partner.
The project is still on-going. The output so far has largely been dissemination; presentations of the technology have been given at the AAPS in New Orleans, & the PDA in Vienna. We are in the process of establishing a facility at De Montfort University for demonstrating the technology to potential end users. A patent is pending for the LyoDEA™technology.