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Basic Theory of Operation
The CMA and CMA-Junior measure a dielectric property of the closure known as the quality factor or Q. The measured Q is correlated to the average free moisture content of a statistically significant number (32) of closures. As a result of such a correlation, the approximate moisture in a given closure can be determined by the CMA and CMA-Junior on a real time basis and displayed as either a histogram - with upper and lower moisture limits - or as a frequency distribution indicating both the mean average moisture and standard deviation (SD). The CMA and CMA-Junior also provides a complete listing of the Q and the determined average moisture values for each of the individual closures measured. An important features of these measurements is that they are rapid (in seconds), nondestructive and done at ambient temperature and humidity. Click on manuscript for a copy the paper that was published in the ISPE Journal in September 2009 to learn more of correlation process.
Sources of Moisture in Closures
The first source of moisture in the closure stems from the closure manufacturing process. The basic formulation of the elastomer will contain a certain amount of moisture. Some but not all of this moisture is removed during the curing process. Therefore the closure supplied by the manufacturer will already contain various amounts of residual moisture depending on the nature of the curing process.
In those cases where the lyophilization will be performed in an aseptic environment, the closure must undergo a sterilization process either by irradiation or steam sterilization. For those closures that are steam sterilized at 121 C at 15 psi for some period of time, additional moisture (free and bound) is absorbed by the closure. It is important to note that the Q value measured by the CMA and CMA-Junior are correlated only to the "free" moisture in the closure.
Effect of Free Closure Moisture on Product Stability
Depending on the composition of the closure, temperature and relative humidity on the sealed vial containing the lyophilized product, the closure can increase the relative humidity in the vial and thus increase the residual moisture in the product that will adversely affect its stability. The process whereby moisture is released from the closure is generally referred to as "outgassing". For some products the outgassing of moisture from the closure can be so severe that the dried product will go back into solution . (See following disappearing cake)
Frequency Distribution of the Dielectric Properties of Closures
The manufacture of elastomer closures is a very complicated and complex process with a host of variables. While the dimensions of the closure can be carefully maintained within close tolerances, there will be changes in such parameters as mass and composition. For that reason there will be a frequency distribution in the dielectric properties of the closures even in the absence of any moisture in the closure. However, it has been shown that an increase in the moisture content will result in a decease in the standard deviation of the frequency distribution of the Q value. This change in the standard deviation with moisture content is the reason for the moisture values determined by the CMA and CMA Junior are considerd a close approximation. However, accuracy and precision of the measured moisture value will increase and the number of points in the correlation data is increased.
An example of the tabular data for ninety 20 mm closures after they had been steam sterilized and dried is shown in the following table.
The CMA and CMA Junior statistically removes the "guess work" out of drying closures
For more technical information concerning the CMA contact Phase Technologies, Inc. by e-mail or phone 610-660-9665. To obtain a quotation for the purchase of a CMA or CMA-Junior.
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