Effects of buffers on spray-freeze-dried/lyophilized high concentration protein formulations.

Abstract

Solid-state protein formulations are known to exhibit enhanced storage stability compared to their liquid dosage form counterparts. pH is one of the factors affecting the stability of protein formulations. The pH of protein formulations in the solution could be influenced by the buffer used, directly impacting their solid-state stability. During lyophilization, buffer components may interact with other formulation components present in the protein formulations, causing a pH shift. This study aimed to investigate the effects of phosphate buffer and amino acid buffers (such as histidine and/or arginine) on the physical properties and accelerated storage stability of spray freeze-dried or lyophilized protein formulations. A model protein, bovine serum albumin (BSA), was used to prepare high-concentration protein formulations. The formulations consisted of BSA, trehalose, and mannitol in an 80:15:5 ratio (w/w), respectively. Various buffers were utilized in the preparation of protein formulations, and the resultant solid formulations underwent screening via accelerated stability study using size exclusion chromatography (SEC). The combination of phosphate and arginine buffers resulted in increased monomer loss in the accelerated storage stability study. Additional characterizations, including solid-state Fourier transform infrared spectroscopy (ssFTIR) and powder X-ray diffraction (PXRD), were conducted. While these analyses did not definitively elucidate the mechanism behind the observed instability, their outcomes provide valuable insights for further investigation, highlighting the need for future research in this area.