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


The FMS 1400 allows the water activity over lyophilized cake samples to be measured directly in a nondestructive manner. As discussed previously, the principal advantage of the FMS 1400 system is the lack of bias introduction that is associated with a sample-vial measuring system, which provides an advantage over using a single measurement chamber for all samples. As the table shows, the FMS 1400 instrument also can be used at a wider range of temperatures than the traditional capacitive-sensor and chilled-mirror techniques. Finally, the FMS 1400 sample vial is not susceptible to the leaking observed with the other two approaches.


Table III: Comparison of three techniques for measuring headspace moisture.
Evaluation of the FMS 1400 instrument performance. Because frequency modulation spectroscopy is a relatively new technique, various operational parameters were evaluated to ensure that the instrument could perform as required for routine investigations and was not limited in use to only research studies. Thus, the suitability of the instrument was evaluated in terms of method specificity, accuracy–linearity, and measurement precision and range.


Table IV: Comparison of moisture retention.
Method specificity. The specificity of the FMS 1400 instrument for moisture measurements was demonstrated by measuring the headspace moisture activity of various saturated salt solutions with known equilibrium moisture activities in the presence of expected container–closure matrix components such as pure N2, pure O2, or room air at various pressures (a low of ~200 Torr versus atmospheric at 760 Torr) under a constant preconditioned temperature of 25 C. A plot of measured RH (%) versus expected RH (%) was generated for each sample type and preconditioned temperature combination, and the slope, y-intercept and R 2 values were calculated for the various salt solutions. Table VI summarizes the results and indicates that container type (i.e., amber versus clear), container size, internal pressure, and preconditioned temperature do not interfere specifically with the measurement of headspace moisture. The observed slopes (0.9–1.1), y intercepts (<5%), and R 2 values (>0.98) are acceptable for the method's intended use. Therefore, we concluded that the method is insensitive to headspace gas composition and has sufficient specificity for headspace moisture.

Accuracy and linearity. The accuracy of the FMS 1400 instrument was evaluated by comparing the mean of the measured relative humidity of freshly made saturated salt solutions with known relative humidity equilibrium values against their expected relative humidity values. Actual and theoretical values were compared at the conditioned temperatures of 25 and 40 C (see Tables VII and VIII). The salt solution with the greatest relative deviation from the expected value at either conditioned temperature is LiCl (~16–19% difference between the expected and actual values). The accuracy obtained is considered sufficient, however, for the method's intended purpose. Linearity, expressed by R 2 in Figures 5a and 5b, was >0.98 and also acceptable.


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