Chief Scientific Officer, Legacy BioDesign LLC
Challenges and Opportunities in the Formulation of Peptide Therapeutics
In many ways, peptides can be more challenging to formulate than globular proteins. There are six specific physicochemical properties than affect their solution behavior and, in turn, their long-term stability in aqueous vehicles. These are (i) maximal chemical instability, (ii) unusual or fluxional higher order structure, (iii) high degree of surface activity, (iv) marked propensity to self-associate, (v) significant solubility in nonaqueous solvents, and (vi) complex aggregation behavior, including proclivity towards gelation. Each of these factors will be discussed in the context of formulation development, as illustrated by the peptide literature. What emerges is the need to consider peptide formulation as a distinct field of activity, not just a subset of protein formulation, although there are some common features.