Water sorption behavior of lyophilized protein-sugar systems and implications for solid-state interactions

This study examines the water sorption behavior of proteins co-lyophilized with sugar/polyol excipients. Gravimetric sorption analysis (GSA) was used to measure water sorption of the lyophilized mixtures and these data allowed for calculation of the water monolayer (M-0). Lyophilized protein-mannitol mixtures behaved as predicted from the data for the pure components. Mannitol was shown to crystallize upon lyophilization. For protein co-lyophilized with sucrose or trehalose, which remain amorphous upon lyophilization, M-0 tended to be lower than that expected based on contributions of the pure protein and sugar. This negative deviation supports the view that amorphous sugars and pharmaceutical proteins interact in the solid state in such a way as to reduce the availability of water-binding sites. At high relative humidities (rh), sucrose and trehalose were susceptible to moisture-induced crystallization. When co-lyophilized protein was present, the GSA data revealed that this crystallization required a higher rh, or did not occur. For the temperature-induced (non-isothermal) sucrose crystallization, which was studied by differential scanning calorimetry, it was found that the temperature of crystallization tended to increase with an increasing amount of protein. The tendency to crystallize rose in the presence of elevated moisture, whether or not protein was present, likely due to the ability of water to plasticize the solid phase. (C) 1998 Elsevier Science B.V. All rights reserved.