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Spray drying is used to produce engineered, inhalable dry powders and is a critical tool for new drug developers. It enables production of powders with a tightly controlled range of particle sizes and solid-state properties. Formulators have control over the crystalline and amorphous character and radial distribution of components and particle morphology. This comes from understanding the impact of each material’s physicochemical properties and the kinetics of droplet drying. 10 April 2023 Inhalation Spray drying to enable new inhaled drug products Concepts and considerations for engineering inhaled powders and their application in next generation therapies Lliralyn M. McEachern, BSc; Thomas S. Lund, BSc and Alan B. Watts, PhD Catalent Pharma Solutions Introduction Spray drying is a well-established technology used to produce engineered, inhalable dry powders and is a critical tool for new drug developers. Typically, powders delivered by dry powder inhalers (DPIs) are composed of either cohesive blends of active phar- maceutical ingredients (APIs) on carrier particles or engineered composite particles [1]. e spray- drying process enables the production of powders with a tightly controlled range of particle sizes and solid- state properties. Formulators have control over the crystalline and amorphous character as well as the radial distribution of components and particle mor- phology [2]. is control comes from understanding the impact of each material's physicochemical prop- erties and the kinetics of droplet drying [3]. ere are many key process inputs and variables that must be considered when designing an inhaled formulation and the associated spray-drying pro- cess. Atomization, solution composition, solvent and excipient selection, and particle collection are some of the factors that have the largest influence on material properties. Since the particle size of the drug product is critical for inhaled therapies, opti- mizing these variables to manufacture particles of the targeted size, with appropriate aerodynamic properties, is a primary objective of respiratory pro- grams. is article discusses ways in which scientists and engineers should consider the variables under their control and expands these considerations into current applications. Process considerations for the spray drying for inhaled powders Atomization Spray drying powders for inhalation requires produc- ing powders with small particle sizes, typically target- ing aerodynamic particle size distribution (APSD) in the range of 1-5 µm in diameter. APSD is one of the most crucial measurements for inhalation products because it predicts deposition region, therapeutic performance and bioavailability of the product [4]. A particle's geometric particle size distribution (GPSD), measured by laser light diffraction, may also be useful as a rapid test for an initial indication of flowability and aerosolization properties [1]. While other parti- cle properties such as morphology, density and sur- face composition also affect APSD, GPSD is often a simple and rapid indicator of APSD. To achieve a particle size suitable for inhalation, two- fluid atomizers are typically used, as they are able to produce smaller particles compared to rotary or pressure nozzles. Two-fluid nozzles, or air atomizing nozzles, have two streams: a gas stream and a liquid stream. e gas stream surrounds the liquid stream, and when they contact each other, the high velocity of the gas stream imparts a shear force on the liq- uid stream and causes atomization. Two-fluid nozzles also allow for tunability of the particle size by adjust- ing the flow rates for either the gas stream or the liq- uid stream. Generally, as the ratio of the atomization gas flow rate to liquid flow rate increases, the particle size decreases [5]. ere are two principal types of two-fluid nozzles: external mixing and internal mixing. Both types have a channel in the center of the nozzle that contains the liquid stream and a surrounding channel that contains the gas stream. For external mixing nozzles, the liquid stream encounters the atomization gas outside of the nozzle and is disrupted and atomized into droplets. In contrast, internal mixing nozzles combine the liquid and gas streams inside the nozzle chamber. Both nozzle types can produce particles in the low micron range. ey also share similar lim- itations, such as low solution flow rates, high atom- ization gas requirements and the potential for wide particle size distributions [6].