The effect of formulation, process and method variables on the reconstitution time in dual chamber syringes

Abstract

Reconstitution time of dried products is influenced by various factors including formulation, process and reconstitution method itself. This manuscript describes factors affecting reconstitution in a dual chamber syringe using highly concentrated huMAb and BSA model formulations. Freezing and drying conditions had only minor impact on the reconstitution time, whereas the primary container and thus the geometry of the lyphilization cake played a major role. Pre-warmed diluent and agitation decreased reconstitution time. For effective agitation, short displacements and high agitation frequencies were found to be desirable conditions to minimize reconstitution time for a given lyophilization cake while foam formation was minimized. The article also provides general strategies (e.g. reduction of lyophilized cake density, use of an optimized fill finish process and suitable method parameters) to reduce reconstitution time, especially for drug product presented in a dual chamber syringe configuration.