Kasraian K, DeLuca P P
University of Kentucky, College of Pharmacy, Lexington 40536-0082, USA.
Pharm Res. 1995 Apr;12(4):491-5. doi: 10.1023/a:1016285425670.
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.
低浓度叔丁醇（TBA）（3 - 10% w/v）的添加被证明会影响冰的晶体习性，导致针状冰晶的形成。这些针状冰晶的升华产生了阻力很小的干燥产品层。使用微量天平技术表明，由于冷冻溶液上方干燥饼的阻力较低，当添加5% w/v TBA时，5% w/v蔗糖溶液的初级干燥阶段显著缩短。在没有TBA的情况下，由于形成了一层表皮，冷冻溶液最初具有约60 cm²托·小时/克的高阻力；一旦表皮破裂，阻力达到10 cm²托·小时/克的恒定值。含有TBA的溶液的干燥产品阻力在0.5 - 3 cm²托·小时/克范围内。在微量天平中，不含TBA时干燥产品所需的总时间为100小时，而含有5% w/v TBA的溶液为10小时。由含有5% w/v TBA的5% w/v蔗糖溶液冻干得到的饼状产品的比表面积为8.57 m²/g，而不含TBA的溶液为0.67 m²/g。向蔗糖溶液中添加TBA不会改变塌陷温度，但升华速度过快使产品从未达到塌陷温度。
