Residual moisture content

Fig. 8. Drying time and rate profiles for leather pasted on glass plates and dried in two temperature stages. Gas velocity = 5 m/s in parallel flow, 71°C in the first stage, 57°C in the second. The falling rate, drying rate is proportional to residual moisture content.

Formaldehyde emission from finished panels is due to the residual formaldehyde present as a gas in the wood and recesses of UF-bonded and MUF-bonded boards as well as dissolved in the boards residual moisture content. On the other... 

The quantitative analysis procedure involves benz extr of TNT, water extr of AN, and taking of the A1 content as insol residue. Moisture content is detd by the Karl Fischer method described in ASTM Method E203-62, except that 8 to lOg samples are added to methanol. Specific gravity is detd by water displacement, and workmanship by visual examination... 

Residual moisture content of samples can play a major role in reproducible sampling of the matrix, as well as in the interaction of the microwave energy with the sample. 

Accelerated aging and crystal transformation rates have also been traced to high residual moisture content. Ando et al. studied the effect of moisture content on the crystallization of anhydrous theophylline in tablets [9]. Their results also indicate that anhydrous materials convert to hydrates at high levels of relative humidity. In addition, if hygroscopic materials (e.g., polyethylene glycol 6000) are also contained in the formulation, needle-like crystals form at the tablet surface and significantly reduce the release rate of the theophylline. 

In addition to the additives used in a formulation to help stabilize the protein to freezing, the residual moisture content of the lyophilized powder needs to be considered. Not only is moisture capable of affecting the physicochemical stability of the protein itself, equally important is the ability of moisture to affect the Tg of the formulation. Water acts as a plasticizer and depresses the Tg of amorphous solids [124,137,138]. During primary drying, as water is gradually removed from the product, the Tg increases accordingly. The duration and temperature of the secondary drying step of the lyophilization process determines how much moisture remains bound to the powder. Usually lower residual moisture in the finished biopharmaceutical product leads to enhanced stability. Typically, moisture content in lyophilized formulations should not exceed 2% [139]. The optimal moisture level for maximum stability of a particular product must be demonstrated on a case-by-case basis. 

Before measuring conductivity, carbon materials and their mixtures were dried to residual moisture content of less than 5wt%. A sample of the investigated material was put into a measuring cell, representing a dielectric cylinder closed at both ends by the measuring electrodes. 

The water is not crystallized to its maximum and can be removed during freeze drying only with difficulty, or not at all. The residual moisture content remains undesirably high. 

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. 

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. 

The storage of a freeze dried product starts with the end of the secondary drying and its transfer into a suitable packing. In the drying plant a certain residual moisture content (RM) is achieved as a function of the product temperature and the drying time (Section 1.2.2). 

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

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).

Table 1.15 Residual moisture content (RM) of different vaccines measured by four different methods.

Willemer, H. Measurements of temperature, ice evaporation rates and residual moisture content in freeze-drying. Developments in Biological Standardization, Vol. 74, p. 123-136. Acting Editors Joan C. May, F. Brown, S. Karger AG, CH-4009 Basel (Switzerland), 1992... 

An example is given in Fig. 2.38 plot 1 is extrapolated to DR < 0.1 %/h. At this time, one more hour drying time would contribute to the desired moisture content of e. g. I % by only 0.1 %. If the computer starts the integration from this calculated time the result is the residual moisture content as a function of time. 

The residual moisture content calculated by this method is called desorbable water, dW. 

This residual moisture content d W (% of the solids) is calculated as shown in Fig. 2.39. The automatic measurement of DR, which is more accurate than a hand operation of the valve and the visual reading of the pressure gauge, supplies additional information about the main drying as shown in Fig. 2.40.1. The same granulate has been dried at the different pc 0.27, 0.44 and 1.46 mbar corresponding to three Tice -27, -24.5 and -15 °C during main... 

The residual moisture content, calculated from DR data, measures the amount of water, which can be desorbed at the product temperature. The procedure corresponds therefore to the thermogravimetric method [1.83] with some practical advantages ... 

Greiff [3.24] studied the stability of purified influenza virus of the strain PR 8 in physiological NaCl solution with calcium lactobionate and human serum albumin (each 1 % in the solution). The freezing rate was approx. 1 °C/min down to -30 °C. During the freeze drying, the product temperature was raised in 12 to 16 h from -30 °C to 0 °C and the product was dried at this temperature. After 24 h, the first 145 vials were removed, and additional vials after intervals of 24 h each. The residual moisture content was 3.0,2.0,1.5, 1.0 and 0.5 %. The stability of the freeze dried virus (expressed in days during which the titer of the infectivity decreased by a factor of 10 was most unfavorable at 0.4 % and 3.2 % RM, (4 and 7 days respectively at +10 °C) and best at 1.7 % RM 145 days or more than 1000 days at -10 °C. 

Fig. 3.22. Shelf temperature (Tsh) as a function of drying time during the freeze drying of bone corticalis and spongiosa and the related residual moisture content (RM).

Merika [3.51] emphasized from his 17 years of experience with the quality control of freeze dried transplants the importance of sterility and residual moisture control as the decisive characteristics. Furthermore, the leak tightness of the storage containers was constantly controlled. Merika did not measure the product temperature during drying, but controled the process by measuring water vapor pressure and temperatures of the shelves and the condenser. The residual moisture content after 2 years of storage must be below 5 %. All products were sterilized by gamma radiation. 

Kapsalis et al. [4.12] showed, that the residual moisture content RM of peas should neither be to small nor too high. During 84 days-storage at +43 °C and RM below 5 %, the thiamine content was barely reduced, but the carotene content fell to approx. 36 %. On the other hand, the thiamine content fell at RM 33 % to 81 %, while 50 % of the carotene content was preserved. These and other reasons not discussed here led Kapsalis to the conclusion, that an optimum RM does generally not exist, but only a desirable RM for one type of product under given storage conditions. 

Fig. 4.5. Peroxide and free fatty acids data as a function the residual moisture content after storage of the dried product for 10 days at +37 °C.

The outer vials are influenced (if the shelf temperature is uniform) by a different temperature of the walls and door of the chamber. If the chamber walls and the door are not kept at shelf temperature, the outer vials must be shielded or they may be too warm during freezing (e. g. freezing differently) or too cold during secondary drying (see Fig. 1.68), and this may lead to a different residual moisture content, from that in inner vials. 

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). 

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