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TDLAS Applications during Lyophilization

Absorption spectroscopy using the diode lasers has been employed to measure the temperatures and concentrations for at least 40 years. Tunable diode laser absorption spectroscopy (TDLAS) utilizes the absorption phenomena to measure the temperature and concentration. The strength of permeated light is related to the absorber concentration according to Lambert-Beer’s law. The temperature and atomic or molecular concentration are determined by the line shape functions and the Boltzmann equation. Based on TDLAS, different molecules such as O2, CH4, H2O, CO, CO2, NH3, HCl, HF, and so on can be detected in situ and continuously with high selectivity and sensitivity. When employing the sensitive detection techniques, the detection limit can be improved to ppm or ppb.


TDLAS can also be employed for velocity measurement using the Doppler effect of light, which can be applicable in the range of near or over the velocity of sound. Due to its reasonable cost and ruggedness, it has been used for mass flow monitoring. With the increasing maturity and broader availability of laser light sources and peripheral electro-optical components, TDLAS has been applied in numerous industrial applications.


The application of TDLAS in the lyophilization field are several:

  • Product temperature at the sublimation interface

  • Product temperature at the bottom center of the vial

  • Product resistance to drying

  • Residual moisture content

  • Primary and secondary drying endpoints

  • Vial heat transfer coefficients

  • Continuous determination of the ice and dryer layer thickness

  • The maximum lyophilizer equipment capability: mass flow as a function of pressure

The LyoFlux™ sensor, manufactured by Physical Sciences Inc. and distributed by SP Scientific, is the only commercial sensor that is capable of accurately and sensitively measuring water vapor mass flow during freeze-drying. It is one of the new tools that are transforming pharmaceutical lyophilization from an art into an efficient, science-based manufacturing process.

LyoFlux™ 200

Compact in design the LyoFlux can be installed and utilized on all sizes of developmental freeze dryers, such as the miniature LyoCapsule and the larger LyoConstellation pilot scale dryer.

A key improvement has been the development of software that allows direct communication between the lyophilizer’s controller and the TDLAS sensor. This communication provides the sensor with automated and continuous measurements of the lyophilizer product in the chamber pressure, shelf temperature and the product temperature data.


The pressure and shelf temperature values provided to the sensor remove the need for user inputs to the sensor throughout the lyophilization process and allow truly autonomous operation of the sensor 24/7/365. This is a big benefit to the end user, saving time, resulting in fewer data collection errors and providing a single location for capturing and plotting the process data subsequent analysis.


Process recipes are input into the lyophilizer and the user initiates the lyophilization cycle, from this point the process runs without operator intervention to apply this technology. At the appropriate time in the process the lyophilizer opens and closes the isolation valve to determine measurement offset values and initiates sensor integration of the mass flow measurements.


The TDLAS sensor measurements and all of the resulting heat and mass transfer model data products calculated using the sensor and lyophilizer data are transferred to the lyophilizer control computer for storage using the data historian. This ensures a common time stamp for all of the data and easier display and processing by the end user.


PSI and SP Scientific continue to explore additional applications and automation of cycle development with the ultimate goal of sensor-based cycle control. Automated cycle control will require many years of additional R&D and industry testing, but achievement of this goal is directly in-line with the FDA Process Analytical Technology (PAT) and Quality by Design (QdD) initiatives.

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