In VitroDosing Performance of the ELLIPTA^®Dry Powder Inhaler Using Asthma and COPD Patient Inhalation Profiles Replicated with the Electronic Lung (eLung™)

Abstract

Background: To evaluate the in vitro dose delivery characteristics of approved asthma and chronic obstructive pulmonary disease (COPD) therapies delivered via the ELLIPTA® dry powder inhaler across inhalation endpoints representative of the target patient population, using the Electronic Lung (eLung™) to replicate inhaler-specific patient inhalation profiles that were previously recorded in vivo.Methods: Selected profiles, representative of the range of inhalation endpoints achieved by patients with all severities of asthma and COPD, were replicated using the eLung breathing simulator in conjunction with an oropharyngeal cast. A Next Generation Impactor was coupled to the eLung to determine the aerodynamic particle size distribution of the ex-throat dose (ETD) of asthma and COPD therapies delivered via the ELLIPTA inhaler. Delivered dose (DD), ETD, and fine particle dose (FPD; defined as a mass of active substance less than 5 μm) were determined for fluticasone furoate (FF)/vilanterol (VI) 100/25 μg and 200/25 μg (asthma and COPD), umeclidinium (UMEC)/VI 62.5/25 μg (COPD only), FF 100 μg and 200μg monotherapy (asthma only), and UMEC 62.5 μg monotherapy (COPD only).Results: Inhalation profiles replicated by eLung covered a wide range of peak inspiratory flow rates (41.6–136.9 L/min), pressure drops (1.2–13.8 kPa), and inhaled volumes through the inhaler (0.7–4.2L). DD was consistent across the range of patient representative inhalation parameters for all components (FF, VI, and UMEC) of each therapy assessed; although ETD and FPD were also generally consistent, some small variation was observed. Dose delivery was consistent for each of the components, whether delivered as mono- or combination therapy.Conclusions: The in vitro performance of the ELLIPTA inhaler has been demonstrated for the delivery of FF/VI, UMEC/VI, FF monotherapy, and UMEC monotherapy. Across a range of inspiratory profiles, DD was consistent, while ETD and FPD showed little flow dependency.

Inhaler Devices for Delivery of LABA/LAMA Fixed-Dose Combinations in Patients with COPD

“…A frequent error of insufficient inhalation effort observed with Diskus Ò in the CRITIKAL study has also been observed with Ellipta Ò . In an in vitro study that replicated inhaler-specific patient inhalation profiles that were previously recorded in vivo using the Electronic Lung (eLung TM ), drug dose delivery via the Ellipta Ò DPI was consistent across the range of patient representative inhalation parameters for all therapies such as formoterol/ vilanterol, umeclidinium/vilanterol, and formoterol [49]. A recent study showed that patients with mild to very severe COPD could also generate sufficient inspiratory flows for optimum drug delivery via Ellipta Ò [50]; it should be noted that this may not always be true in real life.…”

The Ellipta ® in Asthma and Chronic Obstructive Pulmonary disease: Device Characteristics and Patient Acceptability

“…The inspiratory flow rate is an important inhalation profile parameter because of its direct influence on the dose delivery from most DPIs. The Ellipta device produces consistent dose delivery at flow rates over 30L/min [13,15] and this covers the inhalation rates across asthma and COPD disease severity, with even patients who suffer from very severe COPD able to generate an inspiratory effort of 41.6L/min whilst using the inhaler [15,16]. The particle size and fine particle fraction of the Ellipta inhalers vary by the medication delivered.…”

“…In vitro evaluation of drug delivery using patient inhalation profiles captured in vivo demonstrates mean delivery of 77-90% of the blister content depending on the device contents [15]. This results in a pulmonary fraction (Ex-throat dose) of 22.0-42.5% and a fine particle dose of 18.8-37.2%, again depending on blister contents.…”

Novel inhalation devices for treatment of chronic obstructive pulmonary disease

“…Обладает средненизким сопротивлением [16]. Доля частиц оптимального размера, создаваемая уст ройством Эллипта, не зависит от объемной скорости потока на вдохе, по этому показателю Эллипта прак тически не отличается от своего предшественника -устройства Mультидиск.…”

“…Доля частиц оптимального размера, создаваемая уст ройством Эллипта, не зависит от объемной скорости потока на вдохе, по этому показателю Эллипта прак тически не отличается от своего предшественника -устройства Mультидиск. Однако доля частиц опти мального размера у ингалятора Эллипта существен но выше, чем у Мультидиска, и составляет 30-36 % номинальной дозы [16] по сравнению с 20-25 % у Мультидиска [12].…”