High-Concentration Antibody Formulation via Solvent-Based Dehydration.

Abstract

Although subcutaneous (SC) delivery is the preferred administration route for immunotherapies and other biologics for improved patient compliance and lower healthcare costs, it necessitates high-concentration antibody formulations. However, high-concentration antibody solutions face significant instabilities and prohibitively high viscosities. Other approaches for high-concentration formulations have been developed, including non-aqueous solutions, which can be irritating or painful, and antibody-laden hydrogel microparticles, which require centrifugation and are limited to concentrations <300 mg mL^-1. This work presents a new formulation process wherein the antibody is concentrated and encapsulated into hydrogel microparticles via solvent-based dehydration. The final dosage form is an aqueous particle suspension with a formulation concentration of 360 mg mL^-1. In this process, microparticles are synthesized continuously, and antibody precipitation is realized simultaneously to dehydration, which allows for higher antibody concentrations. Antibody phase behavior and precipitation-dehydration kinetics are analyzed. The antibody is structurally and functionally stable in the microparticle post-processing and after 4 months. Injectability of the suspension meets clinical standards with glide force <20 N. For the first time, an aqueous antibody formulation at high concentrations comparable to non-aqueous formulations is presented, ideal for subcutaneous administration. The process is envisioned to be generalizable as a platform for SC delivery in multiple clinical applications.