Abstract
Counterions commonly remain with peptides in salt form after peptide purification. In animal and human studies, acetate counterions are a safer and more acceptable choice for peptides than others (e.g., trifluoroacetate counterions). Various salt forms of caveolin-1 scaffolding domain (CSP7) affect counterion volatilization. The development of lyophilized formulations containing volatile compounds is a challenge because these compounds sublimate away during the process. This work aims to investigate the effect of excipients and lyophilization parameters on the preservation of volatile compounds after lyophilization. The peak areas obtained from 1H and 19F NMR spectra were used to calculate the molar ratio of counterions to CSP7. We found that the pH modifier excipient had the greatest impact on the loss of counterions. By optimizing the molar ratio of bulking agent to CSP7, volatile compounds can be preserved after lyophilization. Higher chamber pressure during lyophilization can lower the sublimation rate of volatile compounds. Moreover, the loss of volatile compounds affects the stability of CSP7 due to the pH shift of reconstituted solutions, thereby causing peptide aggregation. The optimization of the formulation and processing helps preserve volatile compounds, thus minimizing the pH change of reconstituted solutions and maintaining the stability of peptide.
Highlights
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, irreversible, fibrosing disease characterized by defective alveolar epithelial cells which stimulate the migration, proliferation, and activation of mesenchymal cells
We investigated the molar ratios of counterions to CSP7 in lyophilized samples after storage
We found that lyophilization did not affect the presence of TFA counterions. 19F NMR data demonstrate that the molar ratio of TFA to CSP7 in Formulation 2 was constant after three months of storage under the same conditions (Figure 10)
Summary
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, irreversible, fibrosing disease characterized by defective alveolar epithelial cells which stimulate the migration, proliferation, and activation of mesenchymal cells. Incidence has been estimated at 5–16 cases per 100,000 people per year, while its prevalence reportedly ranges from 13 to 20 cases per 100,000 people per year [1,3]. The morbidity rate of IPF is high; 50% of patients die within 3–4 years [3]. Two treatments (pirfenidone and nintedanib) have been approved by the Food and Drug Administration for the treatment of IPF, due to their ability to slow progression of the disease. While current standard of care treatments reduce the incidence of acute exacerbations which often lead to death [7], patients may experience quality of life reducing side effects
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