The effect of tertiary butyl alcohol on the resistance of the dry product layer during primary drying.

The addition of low concentrations of tertiary butyl alcohol (TBA) (3-10% w/v) was shown to influence the crystal habit of ice by causing the formation of needle-shaped ice crystals. The sublimation of these needle-shaped ice crystals resulted in a dry product layer with little resistance. Using a microbalance technique it was shown that the primary drying stage for 5% w/v sucrose solution was considerably shorter when 5% w/v TBA was added due to a lower resistance of the dried cake above the frozen solution. In the absence of TBA the frozen solution had an initially high resistance of approximately 60 cm2 torr hr/gm due to the formation of a skin; once the skin cracked the resistance reached a constant value of 10 cm2 torr hr/gm. The solution containing TBA had a dried product resistance in the range of 0.5-3 cm2 torr hr/gm. The total time required to dry the product in the absence of TBA in the microbalance was 100 hours as compared to 10 hours for the solution containing 5% w/v TBA. The specific surface area of the freeze-dried cake produced from a 5% w/v sucrose solution containing 5% w/v TBA was 8.57 m2/gm as compared to 0.67 m2/gm for solutions not containing TBA. The addition of TBA to the sucrose solution did not change the collapse temperature, but the rapid rate of sublimation prevented the product from ever reaching the collapse temperature.