Non-destructive moisture analysis

by in BPS News, BPS Right Sidebar Content

January 2014

Moisture analysis is one of the most important and basic tests to prove successful freeze drying. There are a variety of moisture analysis methods available, but the majority are slow and destroy the sample, so it’s not feasible to test large numbers of sample for complete batch validation or long-term studies. Any moisture analysis technique that could provide rapid and non-destructive testing would have clear benefits.

Frequency Modulated Spectroscopy

Frequency Modulated Spectroscopy (FMS) is a technique developed by Lighthouse Instruments. Light from a near-infrared diode laser is tuned to match an internal absorption frequency of the water molecule and passed through the empty container headspace above the product. The amount of laser light absorbed is proportional to the moisture concentration in the headspace and the width of the absorption profile gives the total headspace pressure. The measurement method is rapid and non-destructive.  These characteristics allow for multiple measurements on the same sample enabling the accurate monitoring of the oxidation of a single sample over time.  Because the sample is not destroyed there are no waste disposal issues and potentially valuable product can be saved for other tests.


FMS can be used to monitor a number of different stability-related parameters such as moisture, oxygen and pressure. Once calibrated, the analysis takes just a few seconds and can be built into inline monitoring systems.

Applications of FMS include cycle optimisation, shelf mapping and complete-batch moisture inspection for production applications.

In partnership with Lighthouse, Biopharma Technology (BTL) has carried out several studies of the FMS method on freeze-dried materials.

Moisture mapping of a freeze dryer

The rate of drying across a freeze dryer chamber or shelf will vary due to a number of factors including shelf contact, the path of circulating thermal fluid through the shelf, the design of the freeze dryer, and the “edge effect” of radiant heat on the edge of shelves. This will affect the final moisture content achieved in different vials. A random selection of samples across a batch may not give an accurate indication of the real range of final moisture content.

>>Vial headspace moisture in an entire batch

Where is the water?

Water can be present in a number of “forms”, for example free, chemically bound, water of crystallisation. Not all these types may be related to the activity or stability of the product, so it is useful to know not only the overall moisture content but the form and location of the water.

>>Freeze dried cakes: Where is the water?

Lighthouse Instruments FMS

FMS_TmnlThe FMS-1400 Headspace Moisture/Pressure Analyzer is a non-destructive gas analyzer for simultaneously monitoring moisture partial pressure and total headspace pressure.

The analyzer is a robust solid state device and is straightforward to use.  Operators do not require special expertise to run the system meaning the accuracy of measurement does not depend on operator skill.

The benchtop headspace moisture/pressure analyzer can be used for development & QC laboratory applications as well as for at-line in-process control of headspace moisture and pressure levels in production. Systems can be permanently situated in laboratories for product development, release testing, and QC investigations or mounted on carts and wheeled from line to line for in-process monitoring and troubleshooting activities.

Applications include:

• Vacuum leak detection
• Container closure integrity studies
• Moisture determination of lyo product
• Lyo chamber moisture mapping
• Water vapor permeation studies
• Moisture degradation studies
• Stability trends, end-of-shelf life studies

For more information contact Peter Williams:, +44 1962 841092

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