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 human monoclonal antibody and bovine serum albumin model formulations. Freezing and drying conditions had only minor impact on the reconstitution time, whereas the primary container and thus the geometry of the lyophilization cake played a major role. Prewarmed 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.

LAY ABSTRACT: Dried drug products need to be reconstituted to a liquid form before being applied parenteral. Reconstitution time is an important attribute and needs to be as fast as possible in order to serve patients' compliance. Reconstitution time is influenced by various factors including formulation, process, and the reconstitution method itself. The article provides general strategies (e.g., reduction of dried drug product 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. Fast reconstitution of lyophilisates in dual chamber syringe can be achieved by a combination of optimized manufacturing procedures and clear instructions for the end-user (e.g., roll syringe between palms to warm and agitate it to accelerate reconstitution).