Freeze drying cycle lengths

Vries et al. [3.59] described the development of a stable parenteral dosage form of the cytotoxic drug E 09. E 09 dissolves poorly in water and its solution is unstable. With the addition of 200 mg of lactose per vial containing 8 mg of E 09, an optimum formulation was developed with respect to solubility, dosage of E 09 and length of the freeze drying cycle. DSC studies have been used to select the most effective parameters. The freeze dried product remains stable for 1 year when stored at 4 °C in a dark environment. 

Typical lengths of cycles for food stuffs are 5-10 hr, for bacterial pellets 2-20 hr, and for biological fluids 20-50 hr. A production unit with capacity of 500 L may have 75 kW for refrigeration and 50 kW for heating. Conditions for the preparation of freeze dried coffee are preparation of an extract with 20-25% solids, freezing at —25—43°C, sublimation at approx. 200Torr to a final final moisture content of 1-3%, total batch processing time of 6-8 hrs. 

Since we are here concerned mainly with pharmaceutical and, especially, biopharmaceutical freeze-drying, processing costs are of secondary importance. Care must however be taken that limited freeze-drying capacity does not give rise to production problems. Thus, where the total drier capacity threatens to become the limiting factor in the production cycle, the best remedy is to examine whether, and how the cycle length might be reduced, commensurate with the maintenance of an acceptable product quality. This is a problem to which we shall return several times. 

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