Dose Delivery Characterization Of Indacaterol Following Inhalation By COPD Patients

Abstract

Background and RationaleIndacaterol is an investigational, novel, inhaled once-daily long-acting β -agonist for the treatment of chronic obstructive pulmonary 2 disease (COPD). The therapeutic agent is administered as an inhalation dry powder using a new low resistance single dose dry powder inhaler (SDDPI) which will be known as Breezhaler® when approved in Europe. The aim of the present study was to investigate the in vitro dose delivery performance of indacaterol under a range of inspiratory flow rate conditions representing COPD patient use covering mild to very severe disease severity according to the GOLD guidelines. MethodsThe characterization of the aerosol dose of indacaterol delivered to the lungs was performed using a combination of a standard in vitro Next Generation Impactor (NGI) coupled to a flow/volume simulator. The flow/volume simulator enabled simulation of representative patient inspiratory patterns by balancing and modulating the air flow through the inhalation device and auxiliary air to maintain a constant flow rate of 100 L/min through the NGI. Five replicate measurements were conducted for each patient inhalation profile. Six patient profiles (Figure 1) covering mild to very severe stages of COPD were selected from a previously conducted patient inspiratory flow rate study with 26 COPD patients, using the SDDPI device, (Pavkov R, Singh D, Reitveld I., Resp Drug Deliv 2008; 3: 683-686), covering a wide range of inhalation profile parameters (peak flow rate, flow acceleration, inhaled volume, inhalation time). Figure 1: Inhalation Profiles investigated in the study

Recent advances in capsule-based dry powder inhaler technology

“…Due to its low intrinsic internal resistance it requires high inspiratory flow rates (100 and 117 L/min) to obtain a mean pressure drop of 4 kPa within the device [27]. However, Pavkov et al [28] and Singh et al [29] have shown that COPD patients are able to generate a peak inspiratory airflow of approximately 90 L/min through the Breezhaler device, overcoming a pressure drop of approximately 3 kPa. Although performance of DPIs are usually compared at 4 kPa pressure drop [26], studies in COPD patients demonstrated consistent dose delivery from Breezhaler using flow rates between 50 and 100 L/min [28,30] corresponding to a pressure drop less than 4 kPa.…”

Review on Dry Powder Inhalers: Current Advances and Limitations

“…Because of its low characteristic inner opposition it requires high inspiratory stream rates (100 and 117 L/min) to acquire a mean weight drop of 4 kPa inside the gadget [27]. Be that as it may, Pavkov et al [28] and Singh et al [29] have indicated that COPD patients can produce a pinnacle inspiratory wind stream of roughly 90 L/min through the Breezhaler gadget, conquering a weight drop of around 3 kPa. In spite of the fact that presentation of DPIs are generally thought about at 4 kPa pressure drop [26], concentrates in COPD patients exhibited predictable portion conveyance from Breezhaler utilizing stream rates somewhere in the range of 50 and 100 L/min [28,30] comparing to a weight drop under 4 kPa.…”

Nowe Leki w Przewlekłej Obturacyjnej Chorobie Płuc

“…Potwierdzono, że nowe urządzenie podające cząsteczki indakaterolu SD-DPI zapewnia stałą dobrą depozycję leku niezależnie od stopnia ciężkości POChP [11]. Wyniki badania INLIGHT 2, randomizowanego, podwójnie zaślepionego, prowadzonego w grupach równoległych u 1000 chorych na POChP wykazały, że chorzy, którzy otrzymywali 150 µg indakaterolu mieli po 6 miesiącach obserwacji mniej nasiloną duszność, większy efekt rozkurczowy.…”