PFEP for Glucagon and Other Aggregation-Prone Linear Peptides

Glucagon illustrates a central formulation conflict: acidic conditions support initial dissolution but prolonged aqueous storage can produce chemical degradation, aggregation, gelation, and fibrillation, while near-neutral operation may be required in pumps or mixed-hormone devices. This article develops PFEP as a transient aqueous-processing strategy for glucagon and a sequence-based class of linear peptides including exenatide-like, GLP-1-like, and cationic amphipathic molecules. A nucleation-growth model predicts 90.6% soluble monomer after 7 days at 37 °C for a programmed dissolve–desalt–lock process versus 69.8% for direct neutral dissolution. These numbers are synthetic. Applicability is defined by sequence-specific ionization, hydrophobic moment, aromatic content, oxidation/deamidation liabilities, and surface sensitivity; it is not inferred from chain length alone. Article type: Comparative linear-peptide theory with synthetic formulation data. All numerical results labelled synthetic or modelled are hypothesis-illustration and planning outputs, not experimental measurements. No wet-laboratory experiment, validated process, clinical benefit, or shelf life is claimed.