Testing for Moisture in Lyophilized Samples

Introduction - Computrac® Vapor Pro® Rx

The Computrac® Vapor Pro® Rx from AMETEK Brookfield Arizona has been proven to be an ideal instrument for moisture analysis in lyophilized materials, by analyzing the samples in the lyophilization vials without exposing them to ambient air. Sample sizes down to 5 mg can be handled by the Computrac® Vapor Pro® Rx, thanks to the sensitivity of its relative humidity sensor. Moreover, the analysis procedure itself is very simple.

The thermoset polymer capacitor in the Computrac® Vapor Pro® Rx has a selective response to the presence of water like most relative humidity sensors in conventional settings including dry boxes, laboratory controlled environments and houses. The sample is sealed in a vial and then loaded into an oven circulated with an inert gas. When the material is heated, water vapor is evolved off, and transported towards the sensor by the carrier gas.

A quantifiable change in the relative humidity of the sensor chamber occurs during exposure of the sensor to the water vapor. This relative humidity change can be directly translated into the total micrograms of water passing the sensor. THis means the Computrac® Vapor Pro® Rx can analyze lyophilized pharmaceuticals without any requirement of solvents and material processing.

Moisture in Lyophilization Closures

The lyophilization stopper or closure, which prevents the exposure of the lyophilized material to the atmosphere, is often the overlooked source of potential drug quality degradation. The loss in the sample material quality can be high and rapid when the closure fails to perform is role.

Controlling the moisture in the stopper is crucial in ensuring the efficacy of the barrier and the shelf life of the lyophilized material. Moisture released by the closure over time can cause drug degradation, particularly in materials with very low cake weights. The stability of the drug over time can be increased by careful drying of the lyophilization closure.

Drawbacks of Coulometric Karl Fischer Titration

Coulometric Karl Fischer titration is the standard analysis technique for determining moisture in a lyophilization closure. This method involves cutting a batch of closures into pieces and analyzing a representative sample of those cut stoppers for moisture in a coulometric Karl Fischer titrator equipped with an oven.

Coulometric Karl Fischer titration is good for minimizing the influence of slight differences between stoppers on the final moisture analysis result. Nevertheless, cutting the closures adds an additional step prior to performing the analysis and introduces a potential safety risk. Furthermore, the requirement for skilled personnel for operation and maintenance, owing to the involvement of toxic reagents and solvents. is another drawback of this method.

Solution from AMETEK Brookfield Arizona

To address these problems AMETEK Brookfield Arizona, along with some pharmaceutical customers, has designed a procedure for analyzing stoppers on the Computrac® Vapor Pro® Rx that uses whole uncut closures.

This method is not only more convenient when compared to the Karl Fischer titration, it also provides results in good agreement with the KF analysis of the same samples.

Experimental Procedure and Results

To demonstrate the advantage of the new method involving the Computrac® Vapor Pro® Rx, an analysis was performed to test five stopper samples of different size, composition and moisture content on both the KF coulometric titrator equipped with an oven and the Computrac® Vapor Pro® Rx.

The Karl Fischer titration involved cutting the four closures into eight pieces of relatively equal size, followed by mixing the cut pieces and selecting five pieces randomly for the subsequent analysis on the KF Titrator.

The Computrac® Vapor Pro® Rx analysis involved testing a single closure intact for each analysis without additional sample preparation. All samples were analyzed on the Computrac® Vapor Pro® Rx and the Karl Fischer Titrator.

For all samples, the results of the Vapor Pro® analysis were within 65 ppm of the Karl Fischer and the average result on the Vapor Pro® was within the KF margin of error for all analyses (Figure 1). The Vapor Pro® had the added benefit of shorter analysis times of roughly 30min on average when compared to the Karl Fischer of roughly 1 hr.

moisture analysis results for various lyophilization closures

Figure 1. Comparison of moisture analysis results for various lyophilization closures between the Computrac® Vapor Pro® Rx and Coulometric Karl Fischer titration.

Conclusion

For lyophilization closure analysis, the Computrac® Vapor Pro® Rx analysis is an ideal alternative approach to the Karl Fischer titration, yielding comparable results with user-friendly operation and rapid analysis time.

With high durability, the Computrac® Vapor Pro® Rx is also a greener alternative to the Karl Fischer analysis as it does not use solvents or reagents.

Arizona Instrument

This information has been sourced, reviewed and adapted from materials provided by AMETEK Brookfield Arizona

For more information on this source, please visit AMETEK Brookfield Arizona

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Comments

  1. Lindsay Wegiel Lindsay Wegiel United States says:

    What is the method for testing the stopper moisture?  Do you place the whole stopper inside a vial?  What temperature and rate do you use?

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