In Vitro Characterization of the eFlow Closed System Nebulizer with Glycopyrrolate Inhalation Solution

Abstract

Background: Glycopyrrolate administered by a novel, investigational eFlow® Closed System (CS) nebulizer (eFlow CS) is being evaluated for the maintenance treatment of chronic obstructive pulmonary disease (COPD). The eFlow CS is a hand-held, vibrating membrane nebulizer optimized to deliver 1 mL of glycopyrrolate solution into the lung in <3 minutes. Clinical studies have shown improvements in lung function of subjects treated with nebulized glycopyrrolate.Methods: The aerosol performance of the eFlow CS nebulizer was characterized by delivered dose, aerodynamic droplet size distribution and nebulization time. Simulated use nebulizer performance over 60 days was assessed by volume median diameter (VMD), nebulized amount, and nebulization time. Nebulization outputs were assayed to ensure adequate delivery of glycopyrrolate with an acceptable impurity profile. Aerosol condensates were analyzed for glycopyrrolate concentration and impurities by ultra-high-performance liquid chromatography and compared with non-nebulized samples.Results: The mean mass median aerodynamic diameter, geometric standard deviation, and fine particle fraction were 3.7 μm, 1.7, and 72%, respectively, and independent of formulation strength (25 and 50 μg/mL). Delivered dose was 88% of the nominal dose for both formulation strengths. The mean delivered dose, assessed by breathing simulation, was 56.8% for 25 μg/mL and 62.6% for 50 μg/mL. Nebulization times were 1–2.5 minutes with no apparent increasing trend with use over a 60-day period. The nebulized amount showed no significant changes, whereas the VMD showed a slight, but not pharmaceutically relevant, increase (0.1–0.2 μm) after 60-day simulated use. Glycopyrrolate concentration and impurity levels of nebulized samples were statistically similar to those of non-nebulized samples.Conclusion: The eFlow CS generates glycopyrrolate aerosols with high delivered dose, short treatment time, and small droplet size with narrow size distribution suitable for central and peripheral airway deposition. The unit dose vial mitigates medication misuse and ensures dose uniformity. Results support the use of glycopyrrolate/eFlow CS for the treatment of COPD.

Nebulized Glycopyrronium and Formoterol, Budesonide Aerosol Aerodynamic Assessment With Vibrating Mesh and Compressor Air Nebulizer: Anderson Cascade Impactor Study

“…The results of the current studies with active VMN the mean values for fine particle dose (FPD) and Fine particle fraction (FPF) from APSD testing are well within the specified limits including 85 to 115% of the emitted dose from the compressor air nebulizer 17 .The results are also comparable to the APSD testing and results for Glycopyrronium nebulizing solution tested for delivery with eFLOW*Closed System nebulizer that is available in the international market 18,19 .…”

Efficacy and safety of glycopyrrolate/eFlow® CS (nebulized glycopyrrolate) in moderate-to-very-severe COPD: Results from the glycopyrrolate for obstructive lung disease via electronic nebulizer (GOLDEN) 3 and 4 randomized controlled trials

“…SUN-101 (Sunovion Pharmaceuticals Inc., Marlborough, MA) is an inhaled, nebulized glycopyrrolate formulation for use in combination with an innovative eFlow ® Closed System (eFlow ® CS) device (PARI Pharma GmbH; Starnberg, Germany) and does not require the patient to prepare the drug prior to administration. The glycopyrrolate/ eFlow ® CS drugedevice combination produces aerosols with optimized uniform droplet size distributions (3.7 mm mass median aerodynamic diameter, 1.7 geometric standard deviation) and a respirable fraction (72% fine particle fraction) to facilitate central and peripheral airway deposition [23]. Nebulized glycopyrrolate is delivered to the lung within 3 min over multiple tidal breaths rather than a single-breath actuation.…”

<p>The Effect of Baseline Rescue Medication Use on Efficacy and Safety of Nebulized Glycopyrrolate Treatment in Patients with COPD from the GOLDEN 3 and 4 Studies</p>

“…In one such analysis, patient stratification based on baseline use of rescue medications did not impact the efficacy and safety of QVA149 compared with placebo or salmeterol/fluticasone combination. 4 Glycopyrrolate inhalation solution (GLY; Lonhala ® , Sunovion Pharmaceuticals, Inc., Marlborough, MA, USA) 25 µg twice daily (BID) delivered by the eFlow ® Closed System (CS) Nebulizer (Magnair ® , PARI Pharma GmbH, Starnberg, Germany) 5 was approved by the US Food and Drug Administration (FDA) for the long-term maintenance treatment of airflow obstruction in patients with COPD in December 2017. 6 Data from the 12-week, placebocontrolled Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer (GOLDEN) 3 and GOLDEN 4 Phase III studies (NCT02347761 and NCT02347774, respectively) demonstrated statistically significant and clinically important improvements in pulmonary function and patient-reported outcomes (PROs) with GLY compared with placebo in patients with moderate-to-very-severe COPD.…”