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Micro-fluidic Spray Freeze Dried Ciprofloxacin Hydrochloride-Embedded Dry Powder for Inhalation

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Abstract

Active pharmaceutical ingredient (API)-embedded dry powder for inhalation (AeDPI) is highly desirable for pulmonary delivery of high-dose drug. Herein, a series of spray freeze-dried (SFD) ciprofloxacin hydrochloride (CH)-embedded dry powders were fabricated via a self-designed micro-fluidic spray freeze tower (MFSFT) capable of tuning freezing temperature of cooling air as the refrigerant medium. The effects of total solid content (TSC), mass ratio of CH to L-leucine (Leu) as the aerosol dispersion enhancer, and the freezing temperature on particle morphology, size, density, moisture content, crystal properties, flowability, and aerodynamic performance were investigated. It was found that the Leu content and freezing temperature had considerable influence on the fine particle fraction (FPF) of the SFD microparticles. The optimal formulation (CH/Leu = 7:3, TSC = 2%w/w) prepared at − 40°C exhibited remarkable effective drug deposition (~ 33.38%), good aerodynamic performance (~ 47.69% FPF), and excellent storage stability with ultralow hygroscopicity (~ 1.93%). This work demonstrated the promising feasibility of using the MFSFT instead of conventional liquid nitrogen assisted method in the research and development of high-dose AeDPI.

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Funding

This work is financially supported by the National Natural Science Foundation of China (No. 21878197), the Natural Science Foundation of Jiangsu Province (No. BK20180096) and Jiangsu Higher Education Institutions (No. 18KJA530004), the Suzhou Municipal Science and Technology Bureau (No. SYG201810), the Postdoctoral Science Foundation of Jiangsu Province (2021K356C), and the Particle Engineering Laboratory at Soochow University (SDHY2136). Support from the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions was also received.

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  1. Engineering Research Centre of Advanced Powder Technology (ERCAPT), School of Chemical and Environmental Engineering, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, Jiangsu Province, 215123, People’s Republic of China

    Yingjie Chen, Shen Yan, Shengyu Zhang, Quanyi Yin, Xiao Dong Chen & Winston Duo Wu

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  1. Yingjie Chen
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YC: conceptualization, methodology, data curation. SY: validation, visualization, investigation, reviewing, and editing. SZ: validation, visualization, and investigation. QY: validation, data curation, original draft preparation, reviewing, and editing. XDC: validation. WDW: conceptualization, validation, supervision, reviewing, and editing.

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Chen, Y., Yan, S., Zhang, S. et al. Micro-fluidic Spray Freeze Dried Ciprofloxacin Hydrochloride-Embedded Dry Powder for Inhalation. AAPS PharmSciTech 23, 211 (2022). https://doi.org/10.1208/s12249-022-02371-0

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