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 6b: Plot shows percent relative standard deviation versus mean relative humidity for samples at 40 C.
In this experiment, placebo tablets were pre-equilibrated at two humidity levels (at 25 C and 20% RH and at 25 C and 85% RH) for the generation of "dry" and "wet" samples for examination. Measurements first were performed on the dry sample, followed by measurement of the more wet sample, and followed again by a measurement on a fresh dry sample. Ten tablets were used for each measurement, and three replicate measurements were conducted.

The capacitive-sensor technique measurements were conducted in the "quick" mode. Table IV shows the average of the three replicate measurements for each instrument type. On the basis of the average readings obtained following measurement on the final dry sample, the chilled-mirror technique may have a significant moisture retention, and the capacitive-sensor technique may have a moderate moisture retention (likely within the measurement error). Very low bias was observed when the FMS 1400 instrument was used, which is entirely consistent with sealed sample vials being used for the measurements. Thus, the FMS 1400 instrument demonstrated that the potential for bias introduction via moisture retention is not a problem.


Table I: Frequency modulation spectroscopy measurements at 25 C.
Sampling vial and measurement chamber leak rate. The seal integrity of the sampling vial or measurement chamber for each technique also was evaluated. In this experiment, a 1-g desiccant canister was pre-equilibrated at 40 C and 75% RH, and headspace moisture over the desiccant canister was monitored over a 4–8-h period at 40 C. The change in headspace moisture levels over the time course of the measurement then were translated into an effective leak rate on the basis of the desiccant's quantity and moisture-carrying capacity. The moisture leak rates obtained for the various instruments show that the FMS 1400 instrument (<0.05 mg/h) was superior to the other traditional headspace moisture techniques (Rotronics: 0.5 mg/h; Aqualab: 6 mg/h) in terms of the potential for erroneous data generation resulting from moisture egress or ingress during measurement. The FMS 1400 instrument enables long-term measurements to be made, whereas with the other traditional techniques, it will be difficult to obtain reliable data over long time scales without introducing significant error.

Summary comparison of the various techniques. Table V summarizes key attributes of the three headspace-moisture measurement techniques. Comparison points include analysis time, instrument expense, and critical performance variables. As with any instrument comparison, the optimum technique depends on the intended application and the authors' comments should not be taken as an endorsement for any of the instruments.


Table II: Frequency modulation spectroscopy measurements at 40 C.
All three techniques offer comparable analysis times (except in the Rotronic Hygrolab "quick" mode), although they vary greatly in cost (the FMS 1400 instrument is nearly 10 times more expensive than the capacitive-sensor technique and the chilled-mirror technique). In terms of availability, the FMS 1400 instrument is a rather new approach with the greatest research potential of the three, but availability for the instrument may be somewhat limited.


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