Spray drying for pulmonary drug delivery: Comparing two- and three-fluid nozzles for porous particles production

Abstract

The two most common nozzle types used in spray drying (SD) processes are the two (2-FN) and the three-fluid nozzle (3-FN). This study aimed to compare these configurations for the production of inhalable porous particles (PPs) intended for pulmonary drug delivery. Salbutamol sulfate (SS) was selected as a model antiasthmatic drug, while ammonium bicarbonate (AB) served as a pore-forming agent. The influence of nozzle type on drying efficiency, particle characteristics, and aerosolization performance was investigated.A set of optimized conditions for the 2-FN was initially established and then used as a reference to evaluate the 3-FN. Subsequent experiments with the 3-FN explored variations in flow distribution between the internal and outer channels, along with different SS and AB concentrations. Although the 3-FN initially produced larger, less aerodynamic particles, fine-tuning of operating parameters and feed concentrations enabled the production of powders with satisfactory aerodynamic behavior. Remarkably, particles generated with the 3-FN exhibited aerosolization properties comparable to those of the 2-FN despite using up to four times lower concentrations of formulation components. FT-IR analysis confirmed the complete removal of AB post-drying, and long-term stability tests demonstrated preserved particle integrity and aerosol performance after six months of storage. This work provides the first comprehensive comparison of 2-FN and 3-FN for the production of inhalable PPs, unveiling the underexplored potential of 3-FN to generate high-quality inhalable powders under tailored conditions and with markedly lower component concentrations.