Study of the Emitted Dose After Two Separate Inhalations at Different Inhalation Flow Rates and Volumes and an Assessment of Aerodynamic Characteristics of Indacaterol Onbrez Breezhaler\xae150 and 300\xa0\u03bcg

Mohamad Abadelah,Golshan Bagherisadeghi,Gaballa Abdalla,Henry Chrystyn,Hassan Larhrib

doi:10.1208/s12249-017-0841-y

Mohamad Abadelah, Golshan Bagherisadeghi + Show 3 more

Open Access

https://doi.org/10.1208/s12249-017-0841-y

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Abstract

Onbrez Breezhaler® is a low-resistance capsule-based device that was developed to deliver indacaterol maleate. The study was designed to investigate the effects of both maximum flow rate (MIF) and inhalation volume (Vin) on the dose emission of indacaterol 150 and 300 μg dose strengths after one and two inhalations using dose unit sampling apparatus (DUSA) as well as to study the aerodynamic characteristics of indacaterol Breezhaler® using the Andersen cascade impactor (ACI) at a different set of MIF and Vin. Indacaterol 150 and 300 μg contain equal amounts of lactose per carrier. However, 150 μg has the smallest carrier size. The particle size distribution (PSD) of indacaterol DPI formulations 150 and 300 μg showed that the density of fine particles increased with the increase of the primary pressure. For both strengths (150 μg and 300 μg), ED1 increased and ED2 decreased when the inhalation flow rate and inhaled volume increased. The reduction in ED1 and subsequent increase in ED2 was such that when the Vin is greater than 1 L, then 60 L/min could be regarded as the minimum MIF. The Breezhaler was effective in producing respirable particles with an MMAD ≤5 μm irrespective of the inhalation flow rate, but the mass fraction of particles with an aerodynamic diameter <3 μm is more pronounced between 60 and 90 L/min. The dose emission of indacaterol was comparable for both dose strengths 150 and 300 μg. These in vitro results suggest that a minimum MIF of 60 L/min is required during routine use of Onbrez Breezhaler®, and confirm the good practice to make two separate inhalations from the same dose.

Highlights

Inhaled therapy is the mainstay treatment of choice to control the symptoms of asthma and chronic obstructive pulmonary disease (COPD) [1] using either metered dose inhalers (MDIs) or dry powder inhalers (DPIs)
Scanning electron microscopy (SEM) micrographs of the indacaterol formulations are shown in Supplement 1
The particle size distribution (PSD) of indacaterol DPI formulations 150 and 300 μg at different primary pressures measured using a Sympatec HELLOS/RODOS dry dispersion laser diffraction is shown in the figures (Supplements 2 and 3), respectively

Summary

Introduction

Inhaled therapy is the mainstay treatment of choice to control the symptoms of asthma and chronic obstructive pulmonary disease (COPD) [1] using either metered dose inhalers (MDIs) or dry powder inhalers (DPIs). The quality and the amount of the emitted dose from a DPI depend on the patient’s inhalation manoeuvre, the type of device and its formulation [2,3]. The inhaled volume ensures that the dose is emptied from the metering cup/capsule (the latter applies if the DPI is a single-dose capsule product). When inhaling from a single-dose capsule DPI product, it is essential that the inhaled volume is sufficient to empty the entire dose out of the capsule. It is for this reason that the patient information leaflet (PIL) for these DPIs should direct patients to make two separate inhalation manoeuvres from each prepared capsule dose [1,4]

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