The utilization of tertiary butyl alcohol (TBA) as a mass transfer accelerator in lyophilization

Certain materials are not ideal candidates for freeze-drying because of low collapse temperatures. In the presence of 5-10% w/v tertiary butyl alcohol (TBA) these solutions can be freeze-dried rapidly without any sign of collapse. The objective of this research was to define the role of TBA as a mass-transfer accelerator in freeze-drying.; The phase diagram of the TBA-water system was determined and defined using thermal methods. The TBA-water phase diagram is complex and is indicative of compound formation. One can imagine this phase diagram as two simple phase diagrams placed side by side (the water-TBA hydrate system and the TBA hydrate-TBA system).; Freeze-drying experiments, spectral analysis by near-IR, and supporting literature indicate a strong association between TBA and water molecules. The TBA and water molecules form a "clathrate" type complex. This association alters the crystal habit of water during freezing and water freezes as needle-shaped ice crystals. This behavior was observed using a freeze-drying microscope. Upon sublimation of these needle-shaped ice crystals, porous capillary channels are left behind through which water vapor can flow with less resistance. The dried product resistance of 5% sucrose was determined by the microbalance technique. Samples containing TBA had a significantly lower dried product resistance. The collapse of sucrose during freeze-drying was avoided for two reasons. First, the faster rate of sublimation resulted in the maintenance of a lower product temperature (below the collapse temperature). Second, the water content of the partially dried sucrose layer decreases faster in the presence of TBA, so the viscosity of the material increases and hence the viscous flow of the material (collapse) is prevented.; The strong association between TBA and water also caused more water to separate out from the amorphous sucrose phase. This led to less "bound" water and thereby a shorter drying stage.