The project set out to create a new, energy‑efficient continuous atmospheric spray‑freeze‑drying (ASFD) process that could be integrated with a spray‑freezing step producing monodisperse droplets. The research was carried out by a consortium of three partners: the University of Bonn, the German engineering firm GEA Lyophil GmbH, and the engineering consultancy IBL Gesellschaft für Ingenieurdienstleistungen mbH. The university supplied expertise in pharmaceutical lyophilisation formulation and analytical characterisation, GEA contributed its long‑standing experience in designing and building industrial freeze‑drying equipment, and IBL focused on the mechanical and fluid‑dynamic design of the spray system and the droplet generator. The partners worked closely throughout the project, sharing data and prototypes, and the work was organised into parallel work packages that allowed efficient progress.
On the technical side the team first investigated the drying kinetics of spray‑freeze‑dried powders. By varying the spray temperature and the solvent composition they identified optimal conditions that minimise drying time while preserving protein stability. A key finding was that a spray temperature of –15 °C with a tert‑butyl alcohol solution produced fused particles, whereas higher temperatures (up to +15 °C) yielded well‑defined micro‑particles. The use of dimethylsulfoxide as a solvent broadened the range of compatible formulations, enabling the production of amorphous solid dispersions of poorly soluble drugs such as celecoxib. Scanning electron microscopy revealed that ASFD powders had a porous, sponge‑like morphology distinct from conventional freeze‑dried or vacuum‑spray‑freeze‑dried products, which translated into improved dissolution rates.
The droplet generator was a central innovation. The design calculations produced a monodisperse stream with a narrow size distribution, and the prototype was successfully integrated into a laboratory‑scale ASFD unit at GEA. Droplet capture and separation were achieved using a custom collection system that prevented re‑melting and ensured high product yield. The continuous plant design incorporated a two‑stage drying cycle—an initial “main” drying phase followed by a “night” drying phase—to optimise energy use. Early trials on the GEA‑based freeze‑drying tower demonstrated that the continuous ASFD process could achieve drying times comparable to batch freeze‑drying while reducing energy consumption by up to 30 % due to the lower operating temperatures and the elimination of the need for a high‑vacuum stage.
Analytical characterisation confirmed that the ASFD powders retained the bioactivity of sensitive proteins such as lysozyme and bovine serum albumin, with stability profiles similar to conventional freeze‑drying but with a markedly lower thermal load. Flow properties of the resulting powders were evaluated using angle‑of‑repose measurements; 50:50 mannitol‑povidone mixtures showed improved flowability at higher solid loadings compared to conventional formulations, meeting the pharmacopeial criteria for free‑flowing powders.
The project’s outcomes include a validated continuous ASFD plant concept, a scalable droplet generator, and a set of process parameters that enable the production of stable, high‑quality pharmaceutical powders with reduced energy demand. The consortium plans to publish the detailed findings in peer‑reviewed journals and to explore industrial scale‑up opportunities, leveraging the combined expertise of the partners to transition the technology from laboratory to commercial production.