RESOURCE OVERVIEW
Is Mannitol Hemihydrate Detrimental to Protein Stability? Assessing Mannitol Crystallinity in Lyophilized Drug Products.
The high propensity to crystallize during freezing and its high eutectic temperature make mannitol an attractive bulking agent in lyophilized pharmaceuticals. Large molecules, such as proteins, require an amorphous excipient for their stability both during lyophilization and storage. When mannitol is used in protein formulations, the presence of amorphous excipients and protein can inhibit the crystallization of mannitol. Depending on the annealing conditions, they can render mannitol to crystallize in its meta-stable polymorph known as mannitol hemihydrate (MHH, References 1-4). MHH has been shown in the literature to convert into the more stable polymorphs of mannitol (δ-form) during secondary drying or storage by dehydration. The water that is released during dehydration may pose stability threats to the protein.
In this whitepaper, learn from the Simtra BioPharma Solutions team under what conditions MHH dehydrates and how the dehydration impacts protein stability.