Lyoprotectant
An excipient added to a formulation before lyophilisation to protect the peptide from damage during the freeze-drying process. Sugars such as sucrose, trehalose, and mannitol are common lyoprotectants that form a glassy matrix around the peptide, preserving its structure during water removal.
Technical Context
During lyophilisation, water removal can denature peptides by: removing the hydrogen-bonding water shell (hydration layer) that stabilises native conformation, concentrating solutes (increasing ionic strength and changing pH), and subjecting the peptide to ice crystal formation stress. Lyoprotectants counteract these stresses through: water replacement hypothesis (disaccharides like sucrose and trehalose form hydrogen bonds with the peptide surface, replacing the stabilising water shell) and vitrification hypothesis (lyoprotectants form a glassy matrix that physically immobilises the peptide, preventing conformational changes). Optimal lyoprotectant:peptide ratios are typically 100:1 to 500:1 (w/w). The glass transition temperature (Tg) of the lyophilised cake must remain above storage temperature — if Tg is exceeded during storage, the glassy matrix softens and the peptide can degrade. Sucrose (Tg ~75°C) and trehalose (Tg ~115°C) are preferred over mannitol for amorphous glass formation.