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.
Bibliographical noteFunding Information:
(i) Parts of this work were carried out in the Characterization Facility (Linda Sauer and Maria Torija), University of Minnesota, which receives partial support from NSF through the MRSEC program. (ii) The Advanced Photon Source (17-BM; Wenqian Xu and Andrey Yakovenko) was supported by U.S. Department of Energy, Office of Science, Office of Basic Energy Science, under Contract No. DE-AC02-06CH11357. We thank Seema Thakral for her help with the synchrotron X-ray experiments.
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