抄録
Physical properties and protein-stabilizing effects of pharmaceutical excipient combinations in freeze-drying were studied. Frozen solutions containing basic amino acids (e.g., L-arginine) and organic acids (e.g., citric acid) showed thermal transition of maximally freeze-concentrated solute (T_g') that were significantly higher than those of the single-solute frozen solutions. Freeze-drying of solutions containing some basic amino acids and dicarboxylic acids resulted in glass-state amorphous solids that protected secondary structure of bovine serum albumin (BSA) and activity of lactate dehydrogenase (LDH) from lyophilization-induced changes. Thermal analysis and infrared spectroscopy suggested contribution of electrostatic interactions and hydrogen-bonding to decrease mobility of molecules in the glass-state amorphous solids.
