While water is the
solvent of choice for the lyophilization of pharmaceuticals, the addition of an
organic co-solvent can confer several advantages including increased solubility
of hydrophobic drugs, decreased drying time, improved product stability, and
reconstitution characteristics. The objective of this webinar is to demonstrate
the utility of tertiary-butyl alcohol (TBA), a popular co-solvent for
freeze-drying applications. Using a combination of synchrotron X-ray
diffractometry and differential scanning calorimetry, the temperature and
composition of TBA hydrate-water eutectic were identified.
In protein formulations,
a cryoprotectant is generally added to impart stability. Mannitol, a popular
and widely used bulking agent when added to TBA-water systems was retained
amorphous during freezing. Amorphous excipients can provide the necessary
cryoprotection during freezing. Interestingly, mannitol crystallized as the
anhydrous δ-polymorph in the final lyophile. The ability of mannitol to serve
as a cryoprotectant in frozen solutions, and as a bulking agent in the
lyophilized product was demonstrated using human serum albumin (HSA) as the
model protein. This dual functionality of mannitol in presence of TBA provides
a potential avenue for the use of organic co-solvents in frozen and
freeze-dried formulations.