Issue link: https://www.e-digitaleditions.com/i/1496325
12 April 2023 Inhalation ids content in the feedstock is typically kept low to aid in enabling the formation of small particles and is also limited by API and excipient solubility in the selected solvent or solvent blend [5]. Many small molecules have poor water solubility while the standard inha- lation excipients have poor organic solubility. is results in many feedstocks being a blend of water and an organic solvent. An additional consideration is the direct relationship between feedstock solids content and manufacturing output rate. is means that opti- mizing the solids content is critical to balancing man- ufacturability with product performance. Poorly water-soluble compounds can be sprayed as a suspension or an emulsion instead of a solution [9]. Since two-fluid nozzles are often used for spray drying of inhalation products, clogging or blockage of the nozzle liquid orifice is unlikely. ese nozzles typically have liquid feed diameters ranging from 300 µm to greater than 2 mm, which is much larger than the suspension particle size. Prior to spray drying, API particle size is typically reduced by jet- milling or wet-milling techniques to less than 5 µm. Ensuring that the feed tank is well mixed and that settling risk in the feed lines is controlled are critical to ensuring that the product assay is on target and that the collected product is homogenous from start to finish. Emulsions have also been used to engi- neer specific particle morphologies and achieve high drug loads [10]. e temperature of the droplet, and the particle that forms from it, transitions during the drying process, starting at the feedstock temperature. As the drop- let comes into contact with the heated drying gas, it reaches the wet bulb temperature and enters the constant drying rate phase as the droplet shrinks and is cooled by evaporation. e solute begins to con- centrate on the surface of the droplet and as it forms a solid, the temperature progresses to the outlet tem- perature of the spray dryer. is stage is referred to as the falling drying rate phase [7]. e change in drop- let temperature and drying rate during these phases is illustrated in Figure 2. Importantly, while drying of the droplets into particles takes place primarily in the spray-drying chamber at these temperatures, particles held in the collection container are exposed to the temperature and relative saturation conditions within that container. Collection containers can often approach room temperature. For a high throughput aqueous process, room temperature could be below the water dew point, resulting in a high risk of con- densation and water being taken up by the powder. Formulations and solutions Solids loading in the feedstock is impactful for inhala- tion formulations as it contributes to the particle size of the spray-dried powder. For solution feedstocks, weight percentages are often less than 5% solids in solution but may be higher depending on the process- ing conditions and excipients in the formulation. Sol- Figure 2 Theoretical plot of the change in droplet/particle temperature and drying rate over time Constant Rate Period Falling Rate Period Droplet Temperature Drying Rate Outlet Temperature Wet Bulb Temperature