Measurement of the Residual Moisture Content RM

For all measurements of RM the product must be handled in such a way as to exclude water absorption from the surroundings. Filling a freeze dried product into another container and/or weighing it, should only be done in boxes or isolators filled with dry gas (see above). 

The boxes can contain e. g. P205 or be rinsed with dry gas. Handling in the isolator should be done wearing rubber gloves fixed to the isolator. Balances used in such a dry gas need some modifications to avoid electrostatic charges, which could lead to substantial errors. 

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Measurement of the Residual Moisture Content (RM) During the Process... 

By integrating the DR-values it is possible to calculate the residual moisture content (RM). The integral is calculated from the last measurement of DR over time up to any other measured DR. The integral is RM at the time up to which the integral has been calculated. The RM calculated in this way is too small by the amount of water which would have been desorbed after the measured DR. Thus a method of calculation can be deduced The straight line of the DR values is extrapolated until the still desorbable RM is small compared with the RM to be measured. 

Fig. 1.98. Schema of the fiber-optic sensor to measure the residual moisture content (RM) through the bottom of the container with the product.

By integrating the DR values over time it is possible to calculate the residual moisture content (RM). The integral is calculated from the last measurement of DR over... 

Fig. 1.97.1. Schema of the Coulometer MeBzelle DL 36 for measurement of residual moisture content (RM) after Karl Fischer. In the titration cell (1) iodine is electrolytically produced (3) from an iodine-containing analyt (2). Water in the titration cell reacts with the iodine. When the water is used up, a small excess of iodine is produced, which is detected by special electrodes, which leads to iodine production being stopped. The amount of water in the cell can be calculated from the reading of the coulometer, and the amount of electrical charge needed. The solids are introduced into the cell either by a lock, or the water is desorbed in an oven and carried by a gas stream into the cell. 10 pg in a sample can be detected with an accuracy of reading of 0.1 pg (KF Coulometer DL36, Mettler-Toledo AG, CH-8603 Schwerzenbach, Switzerland).

Fig. 1.99. Measured residual moisture content (RM) as a function of the RM data calculated from IR measurements. Within the range from 0.72 % to 4.74 % RM, the error was 0.27 % (Fig. 8 from [1.851).

The residual moisture content of the product in the vials is checked as specified in directive (m). The product in all vials measured has to have an RM 1 % (standard deviation smaller than 0.4 °C. If this is not the case, follow directive (n). 

It should be clear that the RM measured in this way, e. g. 0,1 %, must not be identical with residual moisture contents measured with other methods (see Section 1.3.1) because there will be always some water which cannot be desorbed at the end temperature of the drying. This content of bound water for one product and one temperature is a stable value which can be taken from the measurements of absorption isotherms. 

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