Tailoring Dry Microparticles for Pulmonary Drug Delivery: Ultrasonic Spray Freeze-Drying with Mannitol and Salbutamol Sulphate

Spray freeze-drying has emerged as a viable alternative to traditional spray drying for manufacturing therapeutic dry microparticles. These microparticles exhibit spherical shapes and high porosity, making them ideal for pulmonary drug delivery via dry powder inhalers. However, achieving the right particle size and fine particle fraction is crucial for effective lung deposition. This study employed ultrasonic spray freeze-drying to produce dry microparticles composed of mannitol, either alone or in combination with the bronchodilator salbutamol sulfate. The investigation explored the impact of solid concentration and feed flow rate on particle size, morphology, surface area, porosity, and crystallinity. Increasing the solid concentration and feed flow rate resulted in larger particle sizes. Additionally, the inclusion of the drug led to greater particle size and increased surface area. In vitro drug deposition simulations underscored the influence of solid concentration and feed flow rate on aerodynamic properties. The lowest solid concentration and feed flow rate yielded the highest fine particle fraction and the smallest mass median aerodynamic diameter, owing to lower particle density and smaller geometric size.