Primary chamber pressure

Figure 5 Temperature profile in primary drying of dobutamine HCl-mannitol (1 1), 53 mg solids/mL, 10 mL fill volume. Vials are 5304 molded glass vials (8.3 cm2 cross-sectional area) which are placed in a flat aluminum tray. The heat flux is 42 cal/(cm2 hr), and the chamber pressure is 0.1 torr. (From Ref. 5.)...

Figure 7 The effect of chamber pressure on the rate of primary drying, (a) 0.18 M methylprednisolone sodium succinate 2 mL in molded vials (2.54 cm2), shelf temperature +45°C. (Smoothed data from Ref. 6.) (b) Dobutamine hydrochloride and mannitol (4% w/w in water), 12 mL in tubing vials (5.7 cm2) and shelf surface temperature +10°C. (MJ Pikal. Unpublished data.) (Modified from Ref. 1.)... 

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.

The important and stimulating contributions of Kebarle and co-workers 119 14 > provide most of the data on gas-phase solvation. Several kinds of high pressure mass spectrometers have been constructed, using a-particles 121>, proton- 123>, and electron beams 144> or thermionic sources 128> as primary high-pressure ion sources. Once the solute A has been produced in the reaction chamber in the presence of solvent vapor (in the torr region), it starts to react with the solvent molecules to yield clusters of different sizes. The equilibrium concentrations of the clusters are reached within a short time, depending on the kinetic data for the... 

Fig. 12.12 shows a typical set of flame photographs of a nitropolymer propellant treated with potassium nitrate. From top to bottom, the photographs represent KNO3 contents of 0.68%, 0.85%, 1.03%, and 1.14%. Each of these experiments was performed under the test conditions of 8.0 MPa chamber pressure and an expansion ratio of 1. Though there is little effect on the primary flame, the secondary flame is clearly reduced by the addition of the suppressant The secondary flame is completely suppressed by the addition of 1.14% KNO3. The nozzle used here is a convergent one, i. e., the nozzle exit is at the throat... 

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. 

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. 

The optimum mixture ratio for a given propellant combination is in turn influenced by the other primary design parameters, chamber pressure and expansion ratio. 

The entire system is maintained at 1 inch of water vacuum to prevent toxic materials from escaping into the laboratory. A compressed air ejector causes a negative pressure in the system. A pressure-sensitive alarm connected to the primary chamber sounds an alert if the pressure returns to normal. 

For the LiqgPbj UIW, the total chamber pressure ranges between 0.03 and 0.9 Pa (2 x 10 Torr and 7 x 10 Torr) as liquid temperature increases from 400 to 500°C (Figure 24). Monatomic Li is the primary condensible vapor. Diatomic Li partial pressure is small compared to monatomic Li pressure. The Pb partial pressure is at least a factor of 600,000 lower than... 

During primary drying, the temperature of the product is dependent on shelf temperature and on chamber pressure. The higher the temperature of the shelf, the higher the temperature of the product will be. An increase in chamber pressure favors the thermal exchanges at the gas-product interface and the thermal conductivity from the shelf to the tray. More heat is transported to the product and this results in a rise of product temperature. 

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. 

The chamber pressure during the sublimation step (i.e. the primary drying process) has been found to be related to the product and shelf-surface temperatures [8] however, determining the shelf temperature required is more difficult as it depends on the nature of the heat transfer fluid used to control the shelf temperature and also on the particular design of the freeze-dryer. 

Pressure Primary Chamber Secondary Chamber Burner Gas Combustion Air Venturi Water Separator Tower... 

The relative contributions of the differing heat transfer routes therefore vary with pressure and with vial characteristics. A rise in chamber pressure may lower the product temperature by increasing mass transfer (sublimation) relative to heat input this should be compensated by raising the shelf temperature or, preferably, by adjusting the primary drying time. 

The complex relationship between chamber pressure and temperatures of shelf and product, and its impact on the sublimation rate, is illustrated in Figure 6 for a recombinant protein preparation. " Let us assume that Tg for such a composition is -20°, so that the drying conditions must be set to ensure that the product temperature does not exceed this value at any time during the primary drying cycle. The sublimation rate corresponding to point A, at a chamber pressure of 40... 

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