Dose Delivery Characteristics of the AIR^® Pulmonary Delivery System Over a Range of Inspiratory Flow Rates

Abstract

The purpose of this study was to evaluate the in vitro and in vivo dose delivery characteristics of the AIR pulmonary delivery system over a range of flow rates. A 5-mg placebo powder of engineered particles with low densities (<0.4 g/cc) and large geometric diameters (>5 microm) was delivered via a simple, capsule based, passive dry powder inhaler. The emitted dose, geometric and aerodynamic particle size distributions (aPSDs) were obtained over a range of flow rates (15-60 LPM). The in vitro results demonstrated improved powder dispersion with increasing flow rate through the inhaler. The in vivo dose delivery characteristics were obtained by gamma scintigraphy. Twelve healthy subjects performed the following three inhalation maneuvers: (i) a targeted peak inspiratory flow rate (PIFR) of 20 +/- 10 LPM, (ii) a deep comfortable inhalation, and (iii) a deep forced inhalation. PIFR and inhaled volume were obtained during the inhalation of the dose using a spirometer. In vivo dose delivery was characterized by high and reproducible emitted doses (mean = 87%; inter and intra-subject CV = 5%) and high lung deposition (mean = 51% of the total dose), with low inter and intra-subject CVs (18% and 13%, respectively) across a range of PIFRs (12-86 LPM). Lung deposition of the total dose was shown not to be dependent on PIFR by analysis of variance across the range of inspiratory flow rates (p = 0.29). This was due to the competing effects of smaller aPSDs, increased extrathoracic deposition and higher emitted doses with increasing PIFR. Fully characterizing the effect of inspiratory flow rate requires analysis of the therapeutic response, as well as in vitro dose delivery and lung deposition.

Bridging the Gap Between Science and Clinical Efficacy: Physiology, Imaging, and Modeling of Aerosols in the Lung

“…Instructing patients to inhale at low flow rates has been shown to shift deposition from more proximal to more distal airways. (25)(26)(27) Unfortunately, DPIs and pMDIs use of low inhalation flow rates to reduce inertial impaction is typically compromised by the requirement of reasonably high flow rates needed to fluidize and disaggregate dry powders, (28,29) or by complex interaction between high-speed droplet clouds emitted from pMDIs with enveloping air flow. (19,30,31) Independent of the inhalation flow rate, patients are commonly instructed to perform a breath-hold for several seconds after inhaling, so as to allow aerosols additional time to settle under the influence of gravity in peripheral airways.…”

Large Porous Hollow Particles: Lightweight Champions of Pulmonary Drug Delivery

“…Enhanced dispersibility is reflected in the uniformity of the emitted dose (ED) and fine particle dose [20]. For LPHP formulations, EDs in the range of 80–98% have be achieved, though lower ED values are also reported [9, 21–23]. The upper end of this range represents, as noted by Venbever et al [9], “a strikingly high ED value” compared to ED values obtained from typical aerosol products.…”

Standardized entrainment tubes for the evaluation of pharmaceutical dry powder dispersion

“…Higher volumetric airflow rates are obtained from inhaler devices with lower R D . Higher airflow rates produce higher fine particle fractions (FPF) (Zanen, vanSpiegel, vanderKolk, Tushuizen, & Enthoven, 1992;Smith, Chan, & Brown, 1998;DeLong et al, 2005) and greater lung deposition (Pitcairn, Lunghetti, Ventura, & Newman, 1994;DeLong et al, 2005). Inhaler devices with higher R D are expected to generate greater turbulence and produce higher FPF for a given airflow rate (Srichana, Martin, & Marriott, 1998).…”