Hydroxypropyl-β-cyclodextrin as a multifunctional excipient for enhancing stability and aerosol performance of spray-dried protein formulations.

Protein-based drugs are precise therapeutic options for various refractory lung diseases, significantly improving patient prognosis and quality of life. In this study, a comparative spray-drying approach was employed to prepare inhalable dry-powder formulations of bovine serum albumin (BSA), a surface-active model protein, using established pharmaceutical excipients, including 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), trehalose (Tre), leucine (Leu), and a Tre-Leu combination. The relative performance of HP-β-CD was systematically benchmarked against Tre, Leu, and dual-excipient systems under identical formulation and processing conditions, with respect to protein protection and aerodynamic properties. After 3 months of storage under accelerated stability condition (40 ± 2 °C and 20 ± 5% relative humidity), the protein monomer content in the HP-β-CD-based formulations was marginally lower than that observed in the Tre- and dual-excipient-containing dry powders but still demonstrated effective protein protection. Moreover, the aerosol performance of HP-β-CD formulations surpassed that of other excipients, indicating its superior potential for pulmonary delivery of protein molecules. Overall, this comparative study highlights the potential of HP-β-CD as an alternative excipient for protein-based aerosol dry-powder formulations.