CB-X is a new chemical entity (NCE) with potential therapeutic action in both the upper and the lower respiratory tract. Being a high dosage NCE, drug-alone formulations with appropriate flow properties and distinct aerodynamic deposition profiles were required to potentially support future studies: (i) large particle size (PS) > 5 mm and low fine particle fraction (FPF), and (ii) small PS ~2-3 mm and high FPF.
For that purpose, a particle engineering process for CB-X was developed to enable dry powders with different Particle Size Distributions (PSD), which combined size-reduction by microfluidization with product isolation by spray drying (a process hereinafter designated as wet polishing). It was shown that wet polishing could enable materials in agreement with the defined targets through the same process conditions without negatively impacting the physiochemical properties of the Active Pharmaceutical Ingredient (API). In addition, the dry powders had the required Aerodynamic Particle Size Distribution (aPSD) without the need for any additional excipients as shown by both Fast Screening Impactor (FSI) and Next Generation Impactor (NGI): about 84% w/w of batch 1 consisted of large particles with aPSD > 5 mm; while a FPF of 73% w/w (aPSD < 5 mm) was observed for batch 2.
These results clearly show that wet polishing is a flexible and tuneable particle engineering technology that can be quickly adjusted to formulation drug delivery needs. In addition, the study also demonstrates that FSI can be used to expedite impactor testing during process development stages.