Inhaler devices for chronic obstructive pulmonary disease: insights from patients and healthcare practitioners.

BACKGROUND: The choice of inhaler device for patients with chronic obstructive pulmonary disease (COPD) depends upon multiple attributes. An online survey was devised to assess COPD patients' and healthcare practitioners' (HCPs; physicians and nurses) opinions and preferences for inhaler devices. METHODS: Patients diagnosed with COPD ≥6 months from United States (US), United Kingdom (UK), France, and Germany, and HCPs from the US, UK, France, Italy, and Japan were enrolled to participate in an online quantitative 35 minutes survey. A proprietary analytical tool from Sawtooth Software was used to collect, randomize, and analyze participant opinions and preferences of device attributes, including functionality. RESULTS: A total of 245 patients (mean age, 60.7 years) completed the survey. Of these, 124 and 121 patients were taking fluticasone/salmeterol, and tiotropium, respectively. Patients cited ease of use, dose recording, and dose capacity (single or multi-dose) as important attributes for the device. Key factors that patients considered would make the device easier to use were fewer steps to operate the inhaler, confirmation that the dose has been taken correctly, easier coordination of breathing manoeuver, and least resistance while inhaling. A total of 504 HCPs (380 physicians and 124 nurses) completed the survey, and cited patient satisfaction and ease of use as the most important attributes when selecting an inhaler device for patients. Dose recording and multi-dose versus single-dose designs were given less importance than other attributes such as patient satisfaction and cost by HCPs. CONCLUSION: The survey provides important insights into what patients and HCPs consider to be key attributes of an ideal inhaler device for COPD management. Given that patients with COPD self-administer their COPD chronic medication and need to deliver the correct dose, it is important to consider these insights for the appropriate management of COPD.

In Vitro-In Vivo Correlations Observed With Indacaterol-Based Formulations Delivered with the Breezhaler®.

BACKGROUND: Establishing robust in vitro-in vivo correlations (IVIVC) between aerosol performance, pharmacokinetics, and clinical efficacy is critical in developing bioequivalent drug-device combination products. Recent studies have demonstrated that realistic throat models tested under realistic test conditions may provide good IVIVC with respect to total lung deposition. METHODS: The Alberta idealized throat (AIT) model was utilized with mean peak inspiratory flow rates determined from patient breathing studies. Various formulations of indacaterol (e.g., lactose blends, fixed dose combinations, engineered PulmoSphere™ particles) were tested in the AIT model and in clinical pharmacokinetic studies. RESULTS: Good IVIVC were observed with respect to total lung deposition, systemic delivery, and the contribution of oral absorption to systemic delivery, with percentage differences from the mean in vivo measurements <15%, with most comparisons <5%. CONCLUSIONS: Anatomical throat models represent an exciting tool to aid in formulation development of pharmaceutical aerosols.

Addressing unmet needs in the treatment of COPD.

The burden of chronic obstructive pulmonary disease (COPD) is considerable, both socially and economically. Central to COPD management is the use of long-acting bronchodilators, which provide patients with optimal bronchodilation and improvements in symptoms. The once-daily, long-acting ß2-agonist indacaterol, the long-acting muscarinic antagonist glycopyrronium, and the indacaterol/glycopyrronium fixed-dose combination QVA149 have all been shown to significantly improve lung function and patient-reported outcomes. The ability to take medication appropriately is important. Easy to use, low resistance devices may help patients take their medication and achieve good drug deposition. There is a need to optimise COPD management by treating the right patients with the right therapy at the right time during the course of their disease. Herein, we present a view on the current COPD management landscape and current unmet needs, and look to the future of COPD treatment and how patient care can be optimised.

Delivery characteristics of a low-resistance dry-powder inhaler used to deliver the long-acting muscarinic antagonist glycopyrronium.

OBJECTIVES: The long-acting muscarinic antagonist (LAMA) glycopyrronium (NVA237) has recently been approved as a once-daily treatment for COPD. The objectives of this study were to determine the dose delivery characteristics of glycopyrronium and compare them with those of the LAMA tiotropium, both delivered by their respective capsule-based dry-powder inhalers (DPIs). RESEARCH DESIGN AND METHODS: Seven inhalation profiles derived from patients with moderate and severe COPD were reproduced to determine the aerodynamic particle size distribution of glycopyrronium delivered by the Breezhaler device, a low-resistance DPI†. Theoretical respiratory tract deposition was estimated using a semi-empirical model for healthy lungs. These results were compared with those of tiotropium delivered by the high-resistance HandiHaler‡ device obtained in a previous study using the same set of inhalation profiles. Study limitations are that fine particle fraction (FPF) and particle size are generated by the inhalers are not a direct measure of lung deposition, and the bronchodilator effect of inhaled drugs does not depend solely upon the percentage of the total dose that reaches the lung. RESULTS: The mean FPF (≤4.7 µm) was 42.6% of the nominal dose (which refers to the content of the capsule) for glycopyrronium and 9.8% for tiotropium while the mass median aerodynamic diameter (MMAD) was 2.8 µm and 3.9 µm for glycopyrronium and tiotropium, respectively. The mean estimated intrathoracic drug deposition as a percentage of the mean dose delivered to the Next Generation Impactor was 39% for glycopyrronium and 22% for tiotropium. CONCLUSIONS: The glycopyrronium capsule-based DPI delivered a higher FPF and greater and more consistent intrathoracic deposition irrespective of age and disease severity compared to the tiotropium capsule-based DPI, suggesting that it may be suitable for use by patients with a wide range of COPD severities.

Optimisation of powders for pulmonary delivery using supercritical fluid technology.

Supercritical fluid technology exploited in this work afforded single-step production of respirable particles of terbutaline sulphate (TBS). Different crystal forms of TBS were produced consistently, including two polymorphs, a stoichiometric monohydrate and amorphous material as well as particles with different degrees of crystallinity, size, and morphology. Different solid-state and surface characterisation techniques were applied in conjunction with measurements of powder flow properties using AeroFlow device and aerosol performance by Andersen Cascade Impactor tests. Improved fine particle fraction (FPF) was demonstrated for some powders produced by the SCF process when compared to the micronised material. Such enhanced flow properties and dispersion correlated well with the reduced surface energy parameters demonstrated by these powders. It is shown that semi-crystalline particles exhibited lower specific surface energy leading to a better performance in the powder flow and aerosol tests than crystalline materials. This difference of the surface and bulk crystal structure for selected powder batches is explained by the mechanism of precipitation in SCF which can lead to surface conditioning of particles produced.