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

Abstract

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 Tc-DTPA was inhaled from an Osmohaler™ by healthy human volunteers at 50-70L/min peak inhalation flow rate (PIFR) using both a low and high resistance Osmohaler™, and 110-130L/min PIFR using the low resistance Osmohaler™ (n=9). At 50-70L/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 50-70L/min to 110-130L/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 (R=1.0). On the other hand, the PI had a stronger association with the MMAD (R=1.0) than the FPF (R=0.7). In conclusion the resistance of Osmohaler™ did not significantly affect the total and regional lung deposition at 50-70L/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.

Optimizing Spray-Dried Porous Particles for High Dose Delivery with a Portable Dry Powder Inhaler

“…The flow rate dependence of inhaled mannitol was assessed with the lower resistance version of the Osmohaler (R = 0.021 kPa 0.5 L -1 min) used for bronchoprovocation testing. The decreased from 0.199 mg/mg at a flow rate of 67 L min -1 to 0.098 mg/mg at a mean flow rate of 121 L min -1 , corresponding to a high of -52.0% [67].…”

“…Bronchitol (mannitol inhalation powder) improves mucociliary clearance in CF patients [65][66][67]. The 400 mg nominal dose of mannitol is subdivided into ten size 3 capsules (Vr = 0.30 mL), each containing 40 mg of the powder formulation (packing density = 133.3 mg/mL).…”

“…Bronchitol is manufactured by spray drying a solution of neat mannitol (drug loading = 1.0 mg/mg) to produce fine crystalline drug particles. The aerosol performance of spraydried mannitol with a variant of the RS01 dry powder inhaler (Osmohaler™, R = 0.036 kPa 0.5 L -1 min) was determined by SPECT imaging in nine healthy subjects [67]. The measured was 0.175 mg/mg [67].…”

“…The aerosol performance of spraydried mannitol with a variant of the RS01 dry powder inhaler (Osmohaler™, R = 0.036 kPa 0.5 L -1 min) was determined by SPECT imaging in nine healthy subjects [67]. The measured was 0.175 mg/mg [67]. This leads to a product density of 23.3 mg/mL, and a /capsule of 7.0 mg.…”

A cross-industry assessment of the flow rate-elapsed time profiles of test equipment typically used for dry-powder inhaler (DPI) testing: Part 2– analysis of transient air flow in the testing of DPIs with compendial cascade impactors

“…In the compendial testing of passive DPIs (devices that require inspiratory effort by the patient to function), it is appealing to start the flow by opening the solenoid valve because users of this class of inhaler do something similar (Mitchell, Newman, and Chan 2007). However, this class of inhalers generates and discharges the cloud of particles to the patient in a manner that depends on flow rate (Yang et al 2016). Furthermore, users of DPIs inhale with a wide range of inspiratory profiles (Ramadan and Sarkis 2017), increasing the complexity of making in vitro simulations of real-world use (Mitchell and Suggett 2014;Chrystyn et al 2015).…”