Freeze-Drying of l -Arginine/Sucrose-Based Protein Formulations, Part 2: Optimization of Formulation Design and Freeze-Drying Process Conditions for an l -Arginine Chloride-Based Protein Formulation System

The Influence of Arginine and Counter-Ions: Antibody Stability during Freeze-Drying

“…In summary, this study presented sugar-free Arg based formulations as potential alternative to sucrose or sucrose-containing arginine lyophilisates for biopharmaceuticals, which were already reported in literature. 28,29 While multivalent acids as counter ions enhance T g ' and T g to values above corresponding sucrose formulations and provide good process characteristics, they showed a lack in protein stabilisation. Arginine formulations in combination with the counter ions succinate and lactobionate were comparable in both cake appearance and protein stabilisation efficiency to the sucrose reference formulation.…”

“…Hardly any change was found for ArgCitr-HC, which already exhibited an extremely high T g , and ArgHCl-HC, which was unexpected as an increase was identified in literature. 28 Sugar-free Arg based formulations exhibited extremely high T g values compared to the sucrose reference formulation pointing towards high protein stability in the immobilised amorphous phase. 39,40 In combination with sucrose, T g values were decreased slightly according to a mixed T g based on the Gordon-Taylor equation 10 but the values are still high overall.…”

“…9 The addition of sucrose to arginine formulations resulted in good or better results for particle formation and protein stability compared to the sucrose reference, again similar to previous reports. 28,29 A high mAb concentration of 50 mg/mL resulted in overall low particle counts and ArgLacto-HC turned out to be an interesting formulation candidate next to ArgHCl-HC.…”

“…After 6 months at 40 C antibody formulations containing sucrose and arginine citrate, phosphate or succinate showed more aggregates than those with sucrose and arginine hydrochloride. 28,29 Schersch et al showed a protein stabilising effect of arginine phosphate for lyophilisates which collapsed during freeze-drying. 30 Although, the stabilising potential of amino acids and especially of arginine containing formulations has been shown, a detailed investigation of the stabilising potential of arginine in combination with different counter ions and in the absence of additional excipients is still lacking.…”

“…30 Although, the stabilising potential of amino acids and especially of arginine containing formulations has been shown, a detailed investigation of the stabilising potential of arginine in combination with different counter ions and in the absence of additional excipients is still lacking. 28,29 Therefore, we evaluated sugar-free based solely on arginine in combination with hydrochloride, citrate, lactobionate, phosphate, and succinate as counter ions and compared them to sucrose-based formulations. The formulations were studied with respect to their freeze drying properties, cake characteristics, and stabilisation of a monoclonal antibody (mAb) at 2 mg/mL in the pH range between 5.0 and pH 7.0.…”