Storage

The storage capability of a dried product depends generally on its chemical and structural qualities. The complexity of the problem is highlighted, for example, by the storage stability of therapeutic proteins. The degradation of a protein, the irreversible change in primary structure, conformation or state of aggregation in a glassy surrounding depends on the thermodynamic behaviour of the glass as well as on the qualities of the protein produced during freezing and freeze-drying, as shown by Pikal. The storage temperature of such products has to be well below Tg of the dried formulation; nevertheless unfolding or aggregation of unfolded molecules can occur because of poor interaction between the stable glass structure and movements in protein configurations. From this example some simplified guidelines can be proposed. There are no general rules to estimate the maximum storage time at a maximum tolerable temperature - both depend even on small changes in the formulation of a drug or the variations between two types of fruits or the processing methods of extracts (e.g. coffee). In many cases the maximum storage time is

Figure 9 (A) Desorption rate (DR) as a function of time of a 10% mannitol solution frozen on the shelves of the freeze-drying plant at a rate of0.5-0.8°C min~1. In all runs: 300 vials at an operation pressure (pc) = 0.3 mbar during MD. Runs 1 and 2 at a shelf temperature (Tsh) = 20°C; runs 3 and 4, Tsh = 5°C. Plot 5 egg albumin and plot 6 saccharose for comparison. (B) DR as in A, but the solution is frozen in liquid nitrogen at a rate between 35°C and 66°C min~1. During MD all runs at pc = 0.15 mbar, except run 1 = 0.08 mbar and Tsh in run 1 = — 5°C; in run 2 = 0°C; in runs 3-6 = 0°C for the first 11 h, thereafter until end of MD 10°C. In runs 1-5,126 vials; in run 6, 378 vials. Run 5 intentionally changed from MD to SD 7 h earlier than in runs 3 and 4. (C) DR as in B, but the frozen mannitol was annealed at slightly different temperatures and times:

Figure 9 (A) Desorption rate (DR) as a function of time of a 10% mannitol solution frozen on the shelves of the freeze-drying plant at a rate of0.5-0.8°C min~1. In all runs: 300 vials at an operation pressure (pc) = 0.3 mbar during MD. Runs 1 and 2 at a shelf temperature (Tsh) = 20°C; runs 3 and 4, Tsh = 5°C. Plot 5 egg albumin and plot 6 saccharose for comparison. (B) DR as in A, but the solution is frozen in liquid nitrogen at a rate between 35°C and 66°C min~1. During MD all runs at pc = 0.15 mbar, except run 1 = 0.08 mbar and Tsh in run 1 = — 5°C; in run 2 = 0°C; in runs 3-6 = 0°C for the first 11 h, thereafter until end of MD 10°C. In runs 1-5,126 vials; in run 6, 378 vials. Run 5 intentionally changed from MD to SD 7 h earlier than in runs 3 and 4. (C) DR as in B, but the frozen mannitol was annealed at slightly different temperatures and times:

Run

Annealing temperature (°C)

Annealing time (min)

1

— 24

18

2

— 23.5

18

3

— 26

18

4

— 24.5

18

5

— 24

20

All runs at pc = 0.15 mbar, Tsh in the first 11 h = 0°C, thereafter 10°C, during SD = 30°C except run 1 pc = 0.08 mbar and Tsh =—5°C in the first 11 h. (Reproduced with permission from Haseley and Oetjen, 1999.)

inversely related to the maximum temperature and change during storage and for glassy products the depends strongly on the residual moisture content maximum storage temperature has to be well below

( $ 1% or less can be decisive). For crystallized prod- Tg (see above). The main difference between the stres-

ucts (e.g. antibiotics) the crystal structure must not ses during drying and storage is the length of the

Figure 10 Residual moisture content shown as desorbable water (dW) during secondary drying. Plot 1 = plot 1 in Figure 9B; 2 = 2 (9B); 3 = 3 (9B); 4 = 4 (9B); 9 = 5 (9B); 5 = 2 (9C); 6 = 3 (9C); 7 = 4 (9C); 8 = 1 (9C); 10 = 5 (9C); except run 1, pc = 0.08 mbar and Tsh =-5°C in the first 11 h. (Reproduced with permission from Haseley and Oetjen, 1999.)

Figure 10 Residual moisture content shown as desorbable water (dW) during secondary drying. Plot 1 = plot 1 in Figure 9B; 2 = 2 (9B); 3 = 3 (9B); 4 = 4 (9B); 9 = 5 (9B); 5 = 2 (9C); 6 = 3 (9C); 7 = 4 (9C); 8 = 1 (9C); 10 = 5 (9C); except run 1, pc = 0.08 mbar and Tsh =-5°C in the first 11 h. (Reproduced with permission from Haseley and Oetjen, 1999.)

effective time: a few hours as opposed to many months up to years.

Relaxation time in molecular configurations may be large compared with the drying cycle, but this may be totally different for the long-term storage time. Besides temperature-induced changes, the residual moisture content (RM) can increase the mobility of molecules and promote chemical reactions. The RM at the end of drying can be as specified; nevertheless moisture can diffuse from the stoppers closing the vials into the product, raising the RM by several per cent during storage. Stoppers and the gas in the container of the product have to be dried carefully. On the other hand, 'the drier the better' is unjustified for many products. The Maillard reaction increases with decreasing water activity (aw = p/ps, where p = vapour pressure of the product and ps = saturation vapour pressure) as well as the oxidation of fats. Influ enza virus in a freeze-dried formulation shows the largest decrease in infectivity at 0.4% and 3.2% RM, while at 1.7% it is about 30 times less. Tissue plas-minogen activator and human growth factor in certain formulations are optimally stabilized if they are surrounded by a monolayer of water molecules (which may not be distributed evenly).

Solar Panel Basics

Solar Panel Basics

Global warming is a huge problem which will significantly affect every country in the world. Many people all over the world are trying to do whatever they can to help combat the effects of global warming. One of the ways that people can fight global warming is to reduce their dependence on non-renewable energy sources like oil and petroleum based products.

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