Residual moisture content during process

Oetjen, G. W., 2001. Method of determining residual moisture content during secondary drying in a freeze-drying process. United States Patent No. 6176121 Bl. 

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. 

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. 

The freezing of a product is a very important step. The structure in the frozen product decides whether the product can be freeze-dried at all and under which conditions it can be done. For this reason, the consequences of the freezing rate, layer thickness of the product and excipients are discussed in some detail. The second main point is the measurement and control of the two drying phases the main and secondary drying and the third concentrates on the residual moisture content, its measurement and the consequences during storage of the dry product. There will be critical opinions that some of the processes are unilaterally represented. aim was to show the, hmrts and the advantages ot certain procedures to enable the reader to decide whether the ideas of the quoted authors, or my own can be applied to his tasks. 

Thermal analysis data also dictate the maximum product temperature allowable during primary drying. Shelf temperatures and chamber pressures are then selected to assure that the product remains below this critical threshold temperature during primary drying. Secondary drying conditions necessary to achieve the desired residual moisture content are also identified. Determination of these processing parameters requires numerous process studies and corresponding stability studies to define optimal conditions. 

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

Wet products without a pore system, such as gels, dough, and paste show no pronounced inversion points on their drying rate curves. During the drying process, the rate of drying decreases continuously from an initial value to zero, when the residual moisture content is reached. 

The development of process data in a pilot plant is based on the data and information supplied by the product development. These data will mainly consist of the product qualities, the behavior during freezing and drying, and the container and stopper used. Furthermore the required residual moisture content and the time schedule for the process are provided. 

The performance of ISC units is affected by soil type and soil moisture content. Waste streams derived from ISC processing may consist of volatile off-gases formed during oxidation reactions and products of incomplete oxidation. Bench-scale studies have shown that volatile residuals can be created by ISC, but they have, as yet, not been fuUy characterized. 

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