In Vitro Flow Rate Dependency of Delivered Dose and Fine Particle Dose of Salmeterol/Fluticasone Propionate Easyhaler and Seretide Diskus with Patient Flow Rates Collected in a Randomized Controlled Trial

Abstract

Background: The Easyhaler ® device-metered dry powder inhaler containing Salmeterol and Fluticasone propionate (S/F) has been developed for the treatment of patients with asthma and chronic obstructive pulmonary disease (COPD). We report two studies which evaluated the in vitro flow rate dependence of delivered dose (DD) and fine particle dose (FPD) of S/F Easyhaler versus Seretide Diskus ® . Methods: A randomized controlled trial (RCT) assessed inspiratory flow parameters of S/F Easyhaler and Seretide Diskus in subgroups of patients with asthma (children, adolescents and adults, and elderly) and in COPD patients. The 10th, 50th, and 90th percentile airflow rates were determined and utilized in vitro , to evaluate flow rate dependence of DD and FPD. Flow rate dependence was evaluated relative to the result obtained at the 50th percentile and any values deviating from 100% indicated flow rate dependence. The volumetric flow rate dependence ( Q ) index derived from FPD at 10th and 90th percentile airflows was also evaluated. Results: Overall, 227 patients were enrolled and randomized; 216 completed the RCT. In total, 55.5% of patients were female, and the mean age was 46.3 years. Clinically relevant airflow rates (46, 68, and 85 L/min for S/F Easyhaler and 44, 71, and 96 L/min for Seretide Diskus) were carried forward into the in vitro study, which demonstrated similar flow rate dependence of DD and FPD for S/F Easyhaler compared with Seretide Diskus; all values were within ±15% limits across the 10th, 50th, and 90th percentile airflow rates. Q index results suggested that both S/F Easyhaler and Seretide Diskus are medium airflow-dependent products. Conclusions: Similar in vitro flow rate dependence of DD and FPD was demonstrated for S/F Easyhaler compared with Seretide Diskus, across a range of clinically relevant airflow rates, collected from patients with asthma and COPD.

Understanding Dry Powder Inhalers: Key Technical and Patient Preference Attributes

“…As this was originally intended as a method in quality control in the context of batch release, it is ill suited to produce data relevant to performance with patients. Recent publications are instead reporting the use of fixed ranges of inspiratory flow rates or patient population-specific percentiles when trying to simulate real-life conditions [18, 20, 27]. Haidl et al [28] have suggested criteria for a successful inhalation manoeuvre, namely sufficient device-specific inhalation flow rate, flow acceleration, inhalation volume and inhaled volume after actuation.…”

Consistent Dosing Through the Salmeterol–Fluticasone Propionate Easyhaler for the Management of Asthma and Chronic Obstructive Pulmonary Disease: Robustness Analysis Across the Easyhaler Lifetime

“…The amount of active drug collected into the sampling apparatus was determined by high performance liquid chromatography (HPLC), as described earlier. (15) APSD and FPD. APSD was determined using a nextgeneration impactor (NGI) equipped with a preseparator, in accordance with the European Pharmacopoeia 9.0.…”

“…The NGI results of dropping and vibration tests were also expressed as lg/inhalation for each stage. (15) All analyses were performed using Microsoft Excel (Office Professional Plus 2016; Microsoft Corporation, Redmond, Washington).…”

“…(6,13,15) Both devices had medium air flow dependency based on Q-index (15%-40%). (15,16) A key requirement of CHMP guidance is that product performance should be investigated under conditions that simulate patient use, at the same frequency as indicated in the product label. Based on the regulatory requirements, the aims of this exploratory study were to assess whether the DD and FPD of the S-F Easyhaler remained consistent throughout the inhaler lifespan and under simulated environmental stress conditions, modeled using a variety of in vitro environmental stress tests.…”

Characterization and comparison of Re-Du-Ning aerosol particles generated by different jet nebulizers

“…4 A nebulizer provides a convenient method for the pulmonary delivery of a wide range of drugs, including drug doses too large for delivery by other inhaler devices and combinations of different compatible drugs, especially for the elderly and children's medication. 5,6 Notably, various nebulizers (e.g. conventional jet, ultrasonic and vibrating mesh nebulizers) with different properties are widely used in the clinic.…”