Department of Pharmaceutics, College of Pharmacy, 308 Harvard St. SE, University of Minnesota, Minneapolis, MN 55455, USA.
Pfizer Groton Laboratories, Eastern Point Road, Pfizer Inc., Groton, CT 06340, USA.
Phys Chem Chem Phys. 2020 Jan 21;22(3):1583-1590. doi: 10.1039/c9cp06576h. Epub 2020 Jan 2.
While water is the solvent of choice for the lyophilization of pharmaceuticals, tert-butyl alcohol (TBA) along with water can confer several advantages including increased solubility of hydrophobic drugs, decreased drying time, improved product stability and reconstitution characteristics. The goal of this work was to generate the phase diagram and determine the eutectic temperature and composition in the "water rich" region (0.0 to 25.0% w/w TBA) of TBA-water mixtures. Solutions of different compositions were frozen and characterized by low temperature differential scanning calorimetry and powder X-ray diffractometry (XRD). The thermal events observed during warming, and their characterization by XRD, enabled the generation of phase boundaries as well as the eutectic temperature and composition. While TBA crystallized as a dihydrate in frozen solutions, on heating, the dihydrate transformed to a heptahydrate. TBA heptahydrate and ice (22.5% w/w TBA) formed a eutectic at ∼-8 °C.
虽然水是药物冷冻干燥的首选溶剂，但叔丁醇（TBA）与水结合使用可以带来多种优势，包括增加疏水性药物的溶解度、缩短干燥时间、提高产品稳定性和再配制特性。这项工作的目的是生成相图，并确定 TBA-水混合物中“富水”区域（0.0 至 25.0%w/w TBA）的共晶温度和组成。不同组成的溶液被冷冻，并通过低温差示扫描量热法和粉末 X 射线衍射法（XRD）进行了表征。在升温过程中观察到的热事件及其通过 XRD 的特征分析，使得能够生成相界以及共晶温度和组成。虽然 TBA 在冷冻溶液中结晶为二水合物，但在加热时，二水合物会转化为七水合物。TBA 七水合物和冰（22.5%w/w TBA）在约-8°C 形成共晶。
