The direct administration of drugs to the pulmonary tract offers important advantages for treatment of various local and systemic diseases compared to oral administration. A key challenge for pulmonary drug delivery is to manufacture drug particles with the required properties such that optimal delivery to the site of action can be achieved. A proof of concept of a novel integrated continuous manufacturing process for a pulmonary drug involving continuous anti-solvent crystallization in a segmented flow crystallizer and spray drying is presented. The process parameters that determine the supersaturation ratio in the crystallization process are optimized to obtain sufficient yield and product quality needed for pulmonary administration. Furthermore, ultrasound is applied to improve proce...[ Read more ]

The direct administration of drugs to the pulmonary tract offers important advantages for treatment of various local and systemic diseases compared to oral administration. A key challenge for pulmonary drug delivery is to manufacture drug particles with the required properties such that optimal delivery to the site of action can be achieved. A proof of concept of a novel integrated continuous manufacturing process for a pulmonary drug involving continuous anti-solvent crystallization in a segmented flow crystallizer and spray drying is presented. The process parameters that determine the supersaturation ratio in the crystallization process are optimized to obtain sufficient yield and product quality needed for pulmonary administration. Furthermore, ultrasound is applied to improve process yield by affecting nucleation and reducing encrustation of crystalline material on the inside of the tubular crystallizer. The continuous crystallizer system is integrated with a spray dryer to remove the solvent in the suspension while preserving the crystal product quality. Particle deposition tests of the obtained dry powder shows excellent aerosol performance, which is of crucial importance for pulmonary drug delivery. The presented work demonstrates how integration of crystallization and spray drying in a seamless continuous process can be optimized to produce a dry powder that meets the stringent product quality requirements for pulmonary drug delivery application with a simple and efficient process.