The effect of chamber pressure on heat transfer in the freeze drying of parenteral solutions.

Mechanisms of heat transfer in lyophilization of parenteral solutions are discussed, with emphasis on conduction. Data are presented to demonstrate that the rate limiting resistance to conductive heat transfer is the gas phase resulting from lack of intimate contact between the heat source and the product. Experimental drying curves at constant shelf temperature and various constant chamber pressures reflect the dependence of thermal conductivity of this intervening gas phase, hence the drying rate, on pressure. Deduced values of the resistance of the gas phase at free molecular flow conditions agree with theoretical values. Increasing chamber pressure from 0.04 to 1.3 mm Hg at constant shelf temperature resulted in an increase of about 160% in the primary drying rate. The observed dependence of primary drying rate on pressure points to the need for control of chamber pressure in order to provide for optimum drying conditions and to insure reproducible freeze dry cycles.