# High‐Concentration Antibody Formulation via Solvent‐Based Dehydration

## TL;DR

A new method is developed to create high-concentration antibody formulations suitable for subcutaneous delivery by encapsulating antibodies into hydrogel microparticles.

## Contribution

A solvent-based dehydration process is introduced to achieve high-concentration aqueous antibody formulations without the drawbacks of non-aqueous solutions.

## Key findings

- Antibody-loaded hydrogel microparticles were produced with a concentration of 360 mg/mL.
- The suspension met clinical injectability standards with a glide force under 20 N.
- The antibody remained stable structurally and functionally after processing and storage.

## 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.

Amorphous solid antibodies are encapsulated into hydrogel microparticles through a solvent‐based dehydration process. The solvent extracts water from antibody solution droplets, causing the antibody to concentrate, and precipitation of the antibody into amorphous solid is induced. The particles are resuspended into aqueous solution in which they are injectable for subcutaneous delivery at high concentrations.