Consistent Pulmonary Drug Delivery with Whole Lung Deposition Using the Aerosphere Inhaler: A Review of the Evidence

Abstract

Metered dose inhalers (MDIs) are one of the most common device types for delivering inhaled therapies. However, there are several technical challenges in development and drug delivery of these medications. In particular, suspension-based MDIs are susceptible to suspension heterogeneity, in vitro drug-drug interactions, and patient handling errors, which may all affect drug delivery. To overcome these challenges, new formulation approaches are required. The Aerosphere TM inhaler, formulated using cosuspension delivery technology, combines drug crystals with porous phospholipid particles to create stable, homogenous suspensions that dissolve once they reach the airways. Two combination therapies using this technology have been developed for the treatment of COPD: glycopyrrolate/formoterol fumarate (GFF MDI; dual combination) and budesonide/glycopyrrolate/formoterol fumarate (BGF MDI; triple combination). Here, we review the evidence with a focus on studies assessing dose delivery, lung deposition, and effects on airway geometry. In vitro assessments have demonstrated that the Aerosphere inhaler provides consistent dose delivery, even in the presence of simulated patient handling errors. Combination therapies delivered with this technology also show a consistent fine particle fraction (FPF) and an optimal particle size distribution for delivery to the central and peripheral airways even when multiple drugs are delivered via the same inhaler. Studies using gamma scintigraphy and functional respiratory imaging have demonstrated that GFF MDI is effectively deposited in the central and peripheral airways, and provides clinically meaningful benefits on airway volume and resistance throughout the lung. Overall, studies suggest that the Aerosphere inhaler, formulated using co-suspension delivery technology, may offer advantages over traditional formulations, including consistent delivery of multiple components across patient handling conditions, optimal particle size and FPF, and effective delivery to the central and peripheral airways. Future studies may provide additional evidence to further characterize the clinical benefits of these technical improvements in MDI drug delivery.

The double bronchodilation era: new capabilities in a new drug delivery device

“…Клинический интерес вызвали исследования с использованием гамма-сцинтиграфии и функциональной визуализации органов дыхания. Установлено, что лекарственное соединение ГП/ФФ эффективно откладывается в центральных и периферических дыхательных путях, обеспечивая значимое увеличение ряда показателей внешнего дыхания [32][33][34].…”

The present and future of inhalation therapy for the management of obstructive airway diseases: Emphasis on pressurized metered-dose inhalers

“…Furthermore, the technology is characterized by higher consistency of dose (within a 15% range), irrespective of any shaking-firing delay up to one minute 55,56 . Altogether, these improvements lead to a more efficient lung deposition of the pharmacological compound, compared to both non extra-fine DPIs 57 and suspension pMDIs 58 . Concerning breath-actuated pMDIs, a flow triggered mechanism is incorporated into the device and a spring releases the dose upon activation of that mechanism 59 .…”

Budesonide-Glycopyrronium-Formoterol Fumarate Dihydrate (Breztri Aerosphere)

“…• Missing comparators of potential interest: While ICS inhalers are not indicated by Health Canada for use in patients with COPD, and current COPD guidelines 5,6 do not endorse their use, the clinical expert consulted by CADTH indicated that with the current availability of LABA-LAMA inhalers, patients needing triple therapy who are not adequately controlled on a LABA-LAMA inhaler may be escalated to a LABA-LAMA plus ICS combination. The clinical expert further indicated that the use of an independent ICS inhaler allows for more individualization of ICS dose than the use of an ICS-LABA plus LAMA combination; thus, a separate ICS inhaler may be preferred by some clinicians or patients.…”

“…5 Aerosphere offers advantages over traditional MDIs, such as consistent delivery of drugs across patient conditions, optimal particle size, and effective delivery of the particles to peripheral and central airways. 6 The components of Breztri Aerosphere are available in other formulations that also have Health Canada-approved indications for the management of COPD. 3,4 The objective of this review was to perform a systematic review of the beneficial and harmful effects of budesonide plus glycopyrronium plus formoterol fumarate (BGF) dihydrate inhalation aerosol (Breztri Aerosphere 182 mcg, 8.2 mcg, 5.8 mcg per metered actuation) for long-term maintenance treatment of patients with COPD, to reduce exacerbations of COPD, and to relieve symptoms, including chronic bronchitis and/or emphysema.…”