Formulation Composition and Process Affect Counterion for CSP7 Peptide

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.

Influence of Carbamazepine Dihydrate on the Preparation of Amorphous Solid Dispersions by Hot Melt Extrusion

“…The solution was vortexed for 2 min and transferred to a KF vessel. The weight of the solvate added in the KF vessel was calculated according to Sahakijpijarn et al [44]. The water content of a reference with anhydrous methanol was also measured and subtracted from the sample water content.…”