Strategies to Reduce Reconstitution Time of Lyophilized Biotherapeutics

Lyophilized biotherapeutics with high protein concentration may have long reconstitution times, which pose an inconvenience to the end user. This report describes 2 approaches that lead to reduction of reconstitution time: (1) incorporation of tert-butyl alcohol (TBA) in the prelyophilization formulation and (2) decreased headspace pressure in the final lyophilized vial. Cakes made from prelyophilization formulations containing a range of TBA concentrations were physically characterized. The stability of antibodies with TBA in the liquid and lyophilized states was evaluated under stress conditions. Reconstitution time was minimized (>50% reduction) at a TBA concentration of 5% w/v. Reduced headspace pressure in the lyophilized vial demonstrated greater than 50% reduction in reconstitution time at headspace pressures of less than 50 Torr.