The effect of device resistance and inhalation flow rate on the lung deposition of orally inhaled mannitol dry powder

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• 作者：Michael Y. Yang^a ; Jordan Verschuer^b ; Yuyu Shi^c ; Yang Song^c ; Andrew Katsifis^b ; Stefan Eberl^b ; ^c ; Keith Wong^d ; John D. Brannan^e ; Weidong Cai^c ; Warren H. Finlay^f ; Hak-Kim Chan^a ; ^{kim.chan@sydney.edu.au" class="auth_mail" title="E-mail the corresponding author}
• 关键词：DPI ; Dry powder inhaler ; DTPA ; Diethylenetriaminepentaacetic acid ; FPF ; Fine particle fraction ; FEV1 ; Forced expiratory volume in 1  ; s ; MMI ; Marple Miller Impactor ; MSLI ; Multi-Stage Liquid Impinger ; MMAD ; Mass median aerodynamic diameter ; PIFR ; Peak inhalation flow rate ; PSD ; Particle size distribution ; PI ; Penetration index ; ROI ; Region of interest ; TLD ; Total lung deposition ; USP ; United States pharmacopeia
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：20 November 2016
• 年：2016
• 卷：513
• 期：1-2
• 页码：294-301
• 全文大小：834 K

文摘

The present study investigates the effect of DPI resistance and inhalation flow rates on the lung deposition of orally inhaled mannitol dry powder. Mannitol powder radiolabeled with ^99mTc-DTPA was inhaled from an Osmohaler™ by healthy human volunteers at 50–70 L/min peak inhalation flow rate (PIFR) using both a low and high resistance Osmohaler™, and 110–130 L/min PIFR using the low resistance Osmohaler™ (n = 9). At 50–70 L/min PIFR, the resistance of the Osmohaler™ did not significantly affect the total and peripheral lung deposition of inhaled mannitol [for low resistance Osmohaler™, 20% total lung deposition (TLD), 0.3 penetration index (PI); for high resistance Osmohaler™, 17% TLD, 0.23 PI]. Increasing the PIFR 50–70 L/min to 110–130 L/min (low resistance Osmohaler™) significantly reduced the total lung deposition (10% TLD) and the peripheral lung deposition (PI 0.21). The total lung deposition showed dependency on the in vitro FPF (R² = 1.0). On the other hand, the PI had a stronger association with the MMAD (R² = 1.0) than the FPF (R² = 0.7). In conclusion the resistance of Osmohaler™ did not significantly affect the total and regional lung deposition at 50–70 L/min PIFR. Instead, the total and regional lung depositions are dependent on the particle size of the aerosol and inhalation flow rate, the latter itself affecting the particle size distribution.