The Application of Amino Acids in Freeze Dried Protein Formulations.

The development of freeze dried proteins as a market formulation poses a significant challenge to formulation scientists. The choice of a suitable stabilizer to prevent protein degradation during the process is essential and based on sound knowledge of available excipients and their stabilizing properties. Amino acids have been found to exhibit lyo- and cryoprotective effects similar to those of established stabilizers, such as sugars and/or polymers, but offer a greater diversity of chemical structures and physicochemical properties. Their ability to prevent protein aggregation in the liquid and solid states, as well as their beneficial physicochemical properties in frozen and dried state, may render them a new generation of protein stabilizers for freeze drying. The objective of this review article is to provide a summary of research focused on the application of amino acids in freeze dried protein formulations. In addition to the general physical and chemical properties of proteinogenic amino acids, their thermal properties in the frozen and solid states that are relevant to the freeze drying process are discussed. A review of available stability studies illustrating the application of amino acids to protein formulation design and a discussion of currently known mechanisms contributing to solid-state protein stability in amino acid-based systems are also taken into account.