Formulation Composition and Process Affect Counterion for CSP7 Peptide

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

How Does the Dissimilarity of Screw Geometry Impact Twin-Screw Melt Granulation?

Using a model formulation of 80% gabapentin and 20% hydroxypropyl cellulose (KlucelTM), we investigate how differences in the geometry of mixing elements in the Leistritz Nano-16 and Micro-18 extruders affect granulation mechanisms and the properties of the resulting granules. Two extruders, Leistritz Nano-16 and Micro-18, commonly used in development and manufacturing, respectively, were used. The kneading blocks of the Nano-16 extruder are less efficient in dispersive mixing than the kneading blocks of the Micro-18 due to the thinner discs (2.5 mm wide) of the Nano-16. Therefore, our model formulation could be granulated only under a higher degree of fill (DF) by enhancing the axial compaction and heating of the barrel. In contrast, the thicker (5 mm wide) kneading blocks of the Micro-18 extruder provide efficient dispersive mixing that enables granulation without axial compaction and barrel heating. The higher specific mechanical energy (SME) achieved at higher screw speeds and lower feed rates led to more granulation. Because of the difference in granulation mechanisms between the two extruders, critical processing parameters also differed. Tabletability and degradant content of granules correlated positively with DF for the Nano-16 but with SME for the Micro-18 extruder