Case Study: Lyophilization To Enable Drug Products Containing Labile Molecules

Many therapeutic compounds exhibit limited stability in aqueous solutions due to both chemical degradation processes, such as hydrolysis and oxidation, and physical degradation mechanisms, such as protein aggregation or precipitation. As a result, developing stable liquid formulations for these labile molecules can be a complex, resource-intensive process that may not ultimately yield a product with an adequate shelf life for commercial distribution or clinical use.

To address these challenges, Pace Analytical Life Sciences (Boston) specializes in the development of freeze-dried, or lyophilized, formulations. Lyophilization converts unstable liquid formulations into solid products with significantly enhanced stability, enabling extended storage durations without compromising product integrity or efficacy.

The lyophilization process involves three main steps. First, the formulation is frozen to a temperature below its eutectic point or glass transition temperature, ensuring that all components are immobilized in a solid matrix. Next, during the primary drying phase, the frozen solvent — typically water — is removed by sublimation under reduced pressure. This phase is carefully controlled to maintain the product temperature below the collapse temperature of the formulation, thereby preserving the desired structure and appearance of the final product. Finally, the secondary drying phase removes residual bound water molecules through desorption. This is achieved by gradually raising the product temperature to increase the vapor pressure, driving off remaining moisture, and further stabilizing the product.

By significantly lowering the water content, the rates of most degradation reactions are dramatically reduced. This reduction in chemical and physical degradation pathways results in improved long-term stability of the drug product, making lyophilization a powerful tool for extending the viable shelf life of otherwise unstable therapeutics.