Nanoparticle-containing lyophilized dry powder inhaler formulations optimized using central composite design with improved aerodynamic parameters and redispersibility

Abstract

Objectives: The aim of this study was to improve the aerodynamic behavior and redispersibility of a lyophilized dry powder inhaler (DPI) formulation containing nanoparticles.

Methods: Paclitaxel (PTX)-human serum albumin (HSA) nanoparticles were used as a model, and DPIs containing the nanoparticles were produced by lyophilization using different carriers and carrier ratios. A central composite design was employed to optimize the formulation. L-leucine and mannitol were chosen as independent variables, and mass median aerodynamic diameter (MMAD), emitted fraction, fine particle fraction (FPF), nanoparticle size, polydispersity index (PDI), zeta potential were selected as dependent variables.

Results: The water content of DPIs was less than 5% for all DPIs. The cytotoxicity of the DPIs, determined using A549 cells, was due to PTX alone. Particle sizes of 204.3 ± 1.65 nm and 94.3–1353.0 nm were obtained before and after lyophilization, respectively. The developed method resulted in a reduction in the MMAD from 8.148 µm to 5.274 µm, an increase in the FPF from 17.63% to 33.60%, and an increase in the emitted fraction from 77.68% to 97.03%. The physico-chemical characteristics of the optimized formulation were also assessed.

Conclusions: In conclusion, this study demonstrates that lyophilization can be used to produce nanoparticle-containing DPI formulations with improved redispersibility and aerodynamic properties.

Graphical Abstract

Keywords:

• Dry powder inhaler
• lyophilization
• mannitol
• l-leucine
• human serum albumin
• paclitaxel

Acknowledgements

X-RD, TGA, and SEM analyses were carried out in the Middle East Technical University METU Central Laboratory in Ankara.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.