Freeze chamber pressure

S. L. Nail, The effect of chamber pressure on heat transfer in the freeze drying of parenteral solutions, J. Parenter. Drug Assoc., 34, 358-368 (1980). 

M. J. Pikal, S. Shah, M. L. Roy, and R. Putman, The secondary drying stage of freeze drying drying kinetics as a function of shelf temperature and chamber pressure, Int. J. Pharm., 60, 203-217 (1990). 

Figure 2 The rate of water loss and residual water content during freeze drying. Moxa-lactam disodium formulated with 12% mannitol in aqueous solution at 30% solids 10 mL tubing vials with a solution fill depth of 1 cm. The chamber pressure was 0.05 torr (6.6 Pa). (From Ref. 2.)...

Barriers to heat transfer produce corresponding temperature differences in a freeze-drying system, the actual temperature profile depending upon the rate of sublimation, the chamber pressure, and the container system as well as the characteristics of the freeze dryer employed. An experimental temperature profile is shown in Figure 5 for a system where vials were placed in an aluminum tray with a flat 5 mm thick bottom and a tray lid containing open channels for escape of water vapor. Here, heat transfer is determined by four barriers ... 

Figure 8 An example of the decreasing heat requirement during primary drying at a chamber pressure of 0.15 torr. 5% mannitol maintained at -20°C during primary drying. Results obtained by computer simulation of freeze drying (see Ref. 3). Heavy curve Shelf Fluid. Light curve Shelf surface. Lightweight dashed curve Product Bottom. Heavy dashed curve Sublimation.

Pikal, M. J., Shah, S., Roy, M. L., Putman, R. The secondary stage of freeze-drying Drying kinetics as a function of temperature and chamber pressure. Intern. Journ. of Pharmaceutics, 60, p. 203-217. Elsevier Science Publishers B. V. (Biomedical Division) 1990... 

As compared with a higher pressure and lower shelf temperature outlined in Table 7, drying rates with the reversed conditions of lower pressure and higher shelf temperature would be expected to be slower than the conditions at target shelf temperature and chamber pressure. Compared with those conditions, freezing would be expected to require more time. Primary drying rates would also be reduced because heat transfer rates would be less, product temperatures lower, and residual moisture higher. 

Malinin et al.[3.52] discussed the measurement of RM in freeze-dried bones and compared three methods gravimetry, Karl Fischer titration and NMR spectroscopy. The three methods are discussed in Section 1.3.1. All transplants in this comparison were frozen in LN2 and remained at this temperature for several weeks. The temperature of the condenser during freeze-drying was -60 to -70 °C. The shelves were kept at -30 to -35 °C for the first 3 days. During the last days of the drying the shelf temperature was raised to +25 or to +35 °C. The chamber pressure (p h) was 0.1 mbar. During the initial phase of the process the amount of water vapor transported to the... 

Figure 17 Product temperature and p 20 during freeze-drying of 641 10-mL vials filled with 2.8 mL 3.5% mannitol solution. F, first vial L, last vial O, overfilled (3.3- and 3.8-ml) vial. 1, shelf temperature 2, product temperature 3, chamber pressure 4, / h20-posed end of main drying as indicated by Pnio- (From [17].)...

The functional relationship between product temperature, on the one hand, and shelf temperature and chamber pressure, on the other hand, is affected by many factors including the size and design of the lyophilizer, the characteristics of the product, and the time evolved since the start of primary drying. With a sucrose formulation in vials, we have observed a maximum primary drying product temperature rise of -i-5°C when the shelf temperature was varied from -15 to -i-30°C, whereas a pressure variation from 30 to 250 microbars generated an increase of around -i-2.5°C. With a lactose formulation in ampoules lyophilized in a larger freeze-dryer equipped with a plate-type condenser, the effect of pressure was found to be predominant -i-6.5°C for a pressure move from 50 to 300 microbars, versus -t-l°C for a shelf temperature move from 0° to 25°C. 

When the chamber pressure is controlled by calibrated leaks, the load of product in the freeze-dryer usually plays a minimal role, if any, on the product dry-... 

R. G. Livesey and T. W. G. Rowe, A discussion of the effect of chamber pressure on heat and mass transfer in freeze-drying. J. Parent. Sci. Technol. 4/ 169-171, 1987. 

In most commercial freeze drying processes, chamber pressure, shelf temperature, and time are the only controllable process parameters. Product temperature is not directly controlled. It is the balance between heat and mass transfer that determines the product temperature. Obviously, shelf temperature is important in determining the heat transfer and product temperature. However, because much of the heat is transferred through the gas phase (i.e., collisions of gas molecules with the hot shelf surface and the cold vial bottom), heat transfer as well as mass transfer Eq. (1) is determined, in part, by the chamber pressure. Therefore, product temperature is determined by shelf temperature, chamber pressure, the heat transfer characteristics of the vials, and the mass transfer characteristics of the product and semistoppered vials. 

Fig. 10 Examples of the kinetics of secondary drying. Triangles = mannitol (crystalline) squares = poly (vinylpyrrolidone) circles = moxalactam di-sodium (amorphous). All solids were prepared by freeze-drying a 5% aqueous solution from a 1-cm fill depth, followed by hydration to a uniform moisture level of 7%. The quantity, F, is the fractional attainment of equilibrium, which corresponds to near zero water content. The secondary drying conditions were product temperature = 18°C chamber pressure = 200mTorr. (From Ref °l)...

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