Predicting the amorphous-phase composition during lyophilization

The glass-transition temperature and the composition of the amorphous phase/maximally concentrated solution (classically referred to as Tg' and wg', respectively) as function of added excipients are crucial for the design of lyophilization processes. Whereas the determination of Tg' can be accomplished easily using mDSC, the determination of wg' poses challenges, since the experimental effort needs to be redone for each new excipient mixture (limited transferability of the results possible). In this work, an approach was developed which allows to predict wg' for (1) single excipients, (2) given compositions of a binary excipient mixture, and (3) single excipients in aqueous (model) protein solutions using the thermodynamic model PC-SAFT and one experimental data point of Tg'. Sucrose, trehalose, fructose, sorbitol, and lactose were considered as single excipients. The binary excipient mixture consisted of sucrose and ectoine. The model protein was bovine serum albumin in combination with sucrose. The results reveal that the new approach can precisely predict wg' in the systems considered, including the non-linear course of wg' identified for different sucrose/ectoine ratios. The same applies to the course of wg' as function of the protein concentration. This newly developed approach allows for the reduction of the experimental effort to a minimum.