Abstract
Spray-dried formulations of a hydrophobic, crystalline drug, GDC-A, were prepared using the suspension-PulmoSphere™ technology. Increases in drug loading resulted in decreases in the primary particle size distribution and increases in tapped density. This enabled fine particle doses of up to 25 mg to be achieved with a portable dry powder inhaler from a size three capsule. The powders were physically and chemically stable, with no changes in physical form or degradants observed during processing or on storage in an open configuration at 40°C for 1 month. The potential benefits of the suspension-based spray drying process relative to solution-based spray drying in terms of stability, lung targeting, and safety/tolerability are discussed.
Highlights
Spray drying is a process for converting an atomized liquid feedstock into a dry powder (Vehring, 2008; Vehring et al, 2020)
Spray drying is being increasingly used for the development of moderate and high dose dry powder formulations with total lung doses (TLD) between 1 and 100 mg (Brunaugh and Smyth, 2018; Sibum et al, 2018; Son et al, 2021)
The suspension-based PulmoSphere manufacturing process for GDC-A, including high-shear mixing, high-pressure homogenization and spray drying resulted in purity and related substance profiles that were identical to the neat drug
Summary
Spray drying is a process for converting an atomized liquid feedstock into a dry powder (Vehring, 2008; Vehring et al, 2020). The nature of the feedstock and process conditions play a critical role in determining the size, morphology, physical form, and surface energy of the manufactured particles. For pulmonary delivery, these micromeritic properties are important in controlling the chemical stability, physical stability, manufacturability, aerosol performance, pharmacokinetics, and tolerability of the drug product (Weers and Miller, 2015; Chen et al, 2016; Sahakipijarn et al, 2020; Shetty et al, 2020). GDC-A is a low molecular weight free base drug with a high melting temperature It is highly crystalline, hydrophobic, moderately hygroscopic, and chemically stable with a target TLD between 5 and 20 mg. Pulmonary administration of high doses of a hydrophobic drug presents significant challenges
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