The Process Sequence in Summary - Freeze-drying of Pharmaceuticals and Biopharmaceuticals - page 18

80

60

50

40

0

2 4 6 8 10

Percentage water w/w

Figure 2 The effect of residual water on the long-term (4 years) decomposition to
methaemoglobin of a 6% solution of freeze-dried haemoglobin, formulated with
0.2 M sucrose and stored at 231C

Table 1 Basic energy requirements for the freeze-drying of 1 kg of an aqueous
solution containing 5% solids (sucrose), based on the following
assumptions: ice sublimation is performed at 401C, with a condenser
temperature of 601C (units: kJ kg 1 )

Theoretical energy
needs

Refrigeration
duty

Total energy
needs Operation

500 a Cool/freeze to 401 500 1000

Vacuum pump 2000 2000

Sublimation 2900 2900

7400 b Condense water vapour at

601

3000 10,400

Total 16,300

a Coefficient of performance (COP) of refrigerator ¼ 1.0.
b COP for water vapour condensation ¼ 0.4.

(M.J. Pikal, personal communication). Bearing this in mind, there are
uncertainties as to at what level of residual water the product becomes
''overdried''. In the experience of the author, the so-called overdrying is
not caused by the removal of too much water but by faulty processing
conditions, i.e. not overdrying, but overheating during drying.

2.4 Why Not Freeze-Dry?

The replies resulting from a poll of process managers in pharmaceutical
companies to the question ''Why freeze-dry?'' were discussed in the