In the present investigation freeze-drying of proteins (BSA or trypsin) tog
ether with various carbohydrates, i.e. lactose, sucrose, mannitol, alpha-cy
clodextrin and dextrin, has been studied with particular emphasis on the su
rface composition of the freeze-dried powders. The proteins were found to b
e over-represented on the powder surface as compared to the bulk concentrat
ion of protein. The mechanism behind the surface accumulation is believed t
o be that proteins adsorb preferentially over carbohydrates to the ice/liqu
id interface in the frozen sample. The degree of surface accumulation depen
ded on the carbohydrate used, and was increased in annealed samples compare
d to reference samples. The activity of trypsin was fairly well preserved (
58-90%) in the Freeze-dried powders, but depended on the carbohydrate excip
ient, whilst the surface composition had little effect on the activity. The
activity preservation was improved when the protein concentration was rais
ed from 1 to 10% in the solids. The surface composition of powders containi
ng mixtures of mannitol and dextrin as excipients depended on the ratio bet
ween the two carbohydrates, with the lowest surface coverage of protein obt
ained in 50/50 mixtures. (C) 1999 Published by Elsevier Science B.V. All ri
ghts reserved.