Predicting the amorphous-phase composition during lyophilization.

Area of Science:

• Pharmaceutical Sciences
• Physical Chemistry
• Chemical Engineering

Background:

• Lyophilization process design relies on understanding the glass-transition temperature (Tg ) and maximally concentrated amorphous phase composition (w 'g).
• Experimental determination of w 'g is challenging and requires extensive re-testing for new excipient mixtures.
• Limited transferability of experimental results hinders efficient lyophilization process development.

Purpose of the Study:

• To develop a predictive approach for determining w 'g in lyophilization.
• To enable accurate w 'g prediction for single excipients, binary mixtures, and protein solutions.
• To reduce the experimental effort required for lyophilization process design.

Main Methods:

• Utilized the thermodynamic model PC-SAFT.
• Employed one experimental data point of Tg .
• Applied the model to single excipients (sucrose, trehalose, fructose, sorbitol, lactose), a binary mixture (sucrose/ectoine), and a model protein solution (bovine serum albumin/sucrose).

Main Results:

• The PC-SAFT model accurately predicted w 'g across various systems.
• The model successfully captured the non-linear relationship between w 'g and excipient ratios in binary mixtures.
• Accurate prediction of w 'g as a function of protein concentration was achieved.

Conclusions:

• The developed PC-SAFT based approach provides precise w 'g predictions.
• This method significantly reduces the experimental workload for lyophilization development.
• The approach offers a valuable tool for optimizing lyophilization processes with diverse formulations.