Characterization and suitability of therapeutic antibody dense phases for subcutaneous delivery

Abstract

Subcutaneous antibody dosing formulations comprising solid suspensions have the potential to reduce dosage viscosity and injection volume. Gel beads of three therapeutic antibodies were prepared to determine the feasibility of such formulations. The beads were formed directly from aqueous solution within 0.1-4 days upon addition of biocompatible precipitating agents under conditions compatible with the use of stabilizing excipients. The phase behavior of antibody gel beads and their mechanical characteristics were measured. Gel beads were characterized by reduced elastic moduli of 0.4-1.0 MPa, as measured by atomic force microscopy, and completely redissolved within 10-20 min under physiologic conditions, in vitro. Crystalline particles could also be prepared in some cases and were found to have reduced elastic moduli 3 orders of magnitude greater than those for the gel beads. Both crystalline and gel particles had protein concentrations of 100-180 mg/mL within the dense phase. Protein stored within the dense phase was recoverable after 40 days of incubation at room temperature or 4 °C.