Frequency Modulation Spectroscopy - Pharmaceutical Technology

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Frequency Modulation Spectroscopy
A Novel Nondestructive Approach for Measuring Moisture Activity in Pharmaceutical Samples


Pharmaceutical Technology



Figure 5a: Technique accuracy and linearity at 25 C. Plot shows observed relative humidity versus expected relative humidity at a 25 C conditioning temperature.
Comparison with traditional headspace moisture measurement techniques. A series of experiments was designed and conducted for comparing the FMS 1400 instrument to traditional chilled-mirror and capacitance-sensor techniques. Three areas were identified as most important for this comparison:
  • the measurement of moisture activity in pre-equilibrated tablets to establish a baseline performance of methods for the prevailing sample type in a pharmaceutical setting;
  • moisture retention within the instrument as measured as the bias introduced when a dry sample is preceded by a wet sample;
  • sample measurement chamber leak rate as determined by measurement of change in moisture activity per hour of a wet pre-equilibrated desiccant sample.


Figure 5b: Technique accuracy and linearity at 40 C. Plot shows observed relative humidity versus expected relative humidity at a 40 C conditioning temperature.
One of the fundamental differences between the FMS approach and the other two traditional approaches under examination in the study is that the FMS system uses individual sample vials for each sample that are sealed tightly. The other two approaches use a single sample chamber for all samples.

Comparison of pharmaceutical sample headspace-moisture measurements. Placebo tablets were pre-equilibrated in stability chambers at two RH levels and three temperatures, for a total of six sample treatment conditions: 25 C and 20% RH; 25C and 85% RH; 30C and 35% RH; 30C and 65% RH; 40C and 20% RH; and 40C and 75% RH. Two replicate measurements were performed on 10 tablets using all three headspace-moisture measurement approaches. Headspace-moisture measurements were acquired at 25, 30, and 40 C, with tablets pre-equilibrated at the same respective temperatures. Although the FMS 1400 and chilled-mirror techniques both have in situ temperature control over the sample, the capacitive-sensor technique does not and thus the whole apparatus was housed in an oven for temperature control. The capacitive-sensor technique has two measurement settings that render it possible to perform measurements in a relatively "quick" predictive mode or a "standard" mode. Both modes were evaluated in the study (see Table III). A comparison of the biases obtained shows that traditional headspace-moisture approaches and the FMS 1400 instrument all measure headspace moisture with the same degree of accuracy.


Figure 6a: Plot shows percent relative standard deviation versus mean relative humidity for samples at 25 C.
Measurement bias resulting from instrument moisture retention. The study evaluated the bias introduced when a dry sample is introduced following measurement on a relatively wet sample. Although we expected the bias for the FMS instrument to be nonexistent because an individual sealed sample vial is used for each sample, bias could be a significant issue for the traditional approaches in which all samples must pass through a single sample measurement chamber.


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