Drying product temperature measurement

Fig. 1.76. Product temperature measured in three different locations in the product as function of the drying time. Ticc is measured simultaneously by BTM (Fig. 3 from [1.107]).

Residual moisture is the low level of water, usually in the range of less than 1-3% (wt/wt), remaining in a freeze-dried product after the freeze-drying (vacuum sublimation) process [1-5] is complete. Nail [6] has described in-process methods to monitor the endpoint of freeze-drying using residual gas analysis, pressure rise, comparative pressure measurement, and product temperature measurement. Roy and Pikal [7] used an electronic moisture sensor inside the lyophilization chamber. Residual moisture [8] content is important in the final freeze-dried product because it affects the potency of the product, its long-term stability, and the official shelf life of the product. 

Fig. 4.7 Example of the results obtained during a freeze-drying cycle using various devices to monitor the primary drying stage of 5.5% by weight lactose solution in a pilot-scale freeze-dryer (Barresi et al., 2009a). The freezing stage was run at 223 K for about 5 h, with an initial cooling rate of 1 Kmin while the primary drying was carried out at 263 K, with Pc= 10 Pa (Nv = 713 on tray, Lp = 7.2 X 10 m, dv= 14.2 X 10 m). (a) Bottom product temperature measured by a thermocouple...

Mulhall, P. A., Gieseler, H Schneid, S Pikal, M. J., Schaepman, A., 2008. TDLAS-based mass flux measurements critical analysis issues and product temperature measurements. Proceedings of Freeze-drying of Pharmaceuticals and Biologicals Conference, Breckemidge (CO), USA. 

Tang, X. C., Nail, S. L, Pikal, M. J., 2006a. Evaluation of manometric temperature measurement, a Process Analytical Technology tool for freeze-drying. Part I Product temperature measurement. 

Monomer conversion (79) is followed by measuring the specific gravity of the emulsion. The polymerization is stopped at 91% conversion (sp gr 1.069) by adding a xylene solution of tetraethylthiuram disulfide. The emulsion is cooled to 20°C and aged at this temperature for about 8 hours to peptize the polymer. During this process, the disulfide reacts with and cleaves polysulfide chain segments. Thiuram disulfide also serves to retard formation of gel polymer in the finished dry product. After aging, the alkaline latex is acidified to pH 5.5—5.8 with 10% acetic acid. This effectively stops the peptization reaction and neutralizes the rosin soap (80). 

Experimental conditions and initial rates of oxidation are summarized in Table V. For comparison, initial rates of dry oxidation at the same temperature and pressure of oxygen predicted by Equation 9 are included in parentheses. The predicted dry rate, measured dry rate, and measured wet rates are compared in Figure 2. The logarithms of the initial rates of heat production during wet oxidation increase approximately linearly (correlation coefficient = 0.92) with the logarithm of the partial pressure of oxygen and lead to values of In k = 2.5 and r = 0.9, as compared with values of In k = 4.8 and r = 0.6 for dry oxidation at this temperature. 

If the product temperature approaches T%- from lower temperatures, the viscosity changes rapidly (within a few degrees) by several decimal powers. Since also the product temperature can be measured only with a certain accuracy (see Section 1.2.3), one has to account for both uncertainties. It is recommended that the maximum product temperature during main drying 3 to 5 °C below T. be chosen. 

The increase (I) starts at approx. 16 h and reaches Tsh at approx. 22 h. Secondary drying (SD) has been started (II) at approx. 30 h. Between 16 h and 22 h is no measurable indicator of when to start SD. Also, the safety margin between 22 h and 30 h cannot be connected with the measured product temperature (Fig. 2 from [1.64]). 

Figure 1.84 [1.69] summarizes the measurements of three runs of the product temperatures with RTD, Tice with BTM and of the pressures by CA. The plots show that the difference in pressures during main and secondary drying is largest with no pressure control and still clearly recognized with pc at 0.2 mbar in relation to an ice temperature of approx. -30 °C. 

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. 

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