From single excipients to dual excipient platforms in dry powder inhaler products.

Recent years have seen a marked diversification of excipient based formulation strategies used for the development and commercialisation of dry powder inhaler (DPI) products. These innovative approaches not only provide benefits to patients and health care professionals through the availability of a wider range of therapeutic DPI products, but, importantly, also allow formulators to exploit the potential opportunities that excipients provide for the development of DPIs. Whilst many DPI products have, and continue to be developed using a single formulation excipient, the commercialisation of DPI products which contain the two excipients lactose monohydrate and magnesium stearate, namely the 'dual excipient platform' has recently been achieved. This article provides an overview of the background and current status of the development of such 'dual excipient platform' based DPI products.

Characteristics of a capsule based dry powder inhaler for the delivery of indacaterol.

OBJECTIVE: To report performance characteristics and robustness of the Breezhaler device, a new capsule based dry powder inhaler (DPI) with low resistance (0.07 cm H(2)O(½)/L/min) facilitating high inspiratory flow rates. This device was developed to deliver the novel, inhaled once-daily ultra long-acting ß(2)-agonist indacaterol, formulated as an inhalation powder in a capsule, and other investigational drugs including NVA237 and QVA149. RESEARCH DESIGN AND METHODS: Peak inspiratory flow rates via the DPI device were determined in patients with chronic obstructive pulmonary disease (COPD) using an Inhalation Profile Recorder. The flow-rate dependency of the in vitro performance (delivered dose and fine particle mass) of indacaterol in the DPI device was examined. Data on patient experience were captured throughout the indacaterol phase III registration program, and the robustness of the device was investigated after mechanical stress. RESULTS: Twenty-six patients with COPD that ranged from mild to very severe were recruited (aged 49-84 years); 25 patients were able to generate flow rates in excess of 60 L/min via the DPI device. The mean delivered dose of indacaterol (150 and 300 µg) remained within 15% of the target dose, with a consistent fine particle mass at flow rates of 50-100 L/min. In the indacaterol registration program, patients with mild to very severe COPD were able to use the device successfully, with a low device complaint rate (<0.03%) and no device failures from approximately 90,000 devices. In mechanical stress tests, drop testing resulted in, at most, only cosmetic damage, with no effect on the delivered dose. CONCLUSION: The capsule based DPI device is a low resistance device, suitable for use by patients with a wide range of COPD severities, delivering a consistent dose irrespective of disease severity and age. The device provided consistent delivery of indacaterol with no reported device failures in clinical trials.

Minimizing variability of cascade impaction measurements in inhalers and nebulizers.

The purpose of this article is to catalogue in a systematic way the available information about factors that may influence the outcome and variability of cascade impactor (CI) measurements of pharmaceutical aerosols for inhalation, such as those obtained from metered dose inhalers (MDIs), dry powder inhalers (DPIs) or products for nebulization; and to suggest ways to minimize the influence of such factors. To accomplish this task, the authors constructed a cause-and-effect Ishikawa diagram for a CI measurement and considered the influence of each root cause based on industry experience and thorough literature review. The results illustrate the intricate network of underlying causes of CI variability, with the potential for several multi-way statistical interactions. It was also found that significantly more quantitative information exists about impactor-related causes than about operator-derived influences, the contribution of drug assay methodology and product-related causes, suggesting a need for further research in those areas. The understanding and awareness of all these factors should aid in the development of optimized CI methods and appropriate quality control measures for aerodynamic particle size distribution (APSD) of pharmaceutical aerosols, in line with the current regulatory initiatives involving quality-by-design (QbD).

Inhalation devices for long-acting beta2-agonists: efficiency and ease of use of dry powder formoterol inhalers for use by patients with asthma and COPD.

BACKGROUND: Since the long-acting beta(2)-agonist bronchodilator, formoterol, first became available for the treatment of subjects with asthma or chronic obstructive pulmonary disease (COPD), generic forms of this agent have been launched in a variety of devices. It is timely to review the characteristics of the original dry powder delivery device, the single-dose Aerolizer, its in vitro performance and its comparability with other inhaler devices that are now available for delivery of formoterol. SCOPE: This review focuses on the performance of the formoterol Aerolizer inhaler in comparison with other inhalers. Publically available data (PubMed) on the device performance characteristics of the Aerolizer were reviewed and summarized, together with the results of comparative studies performed by the authors. Published studies (PubMed) on patient handling and inhaler technique that include the Aerolizer are described and studies comparing the clinical effect of formoterol in the Aerolizer with formoterol delivered via other devices were reviewed and are summarized. FINDINGS: The Aerolizer performs consistently in dosing efficiency across a range of inspiratory flow rates, suggesting its suitability for use by patients with differing inspiratory flow abilities. The single-dose, capsule-based nature of the device provides patients with obvious feedback on whether the drug has been taken successfully and the Aerolizer has been shown to be one of the more easily used devices in comparative patient handling studies. Studies comparing the clinical effect of formoterol delivered by different inhalation devices show that formoterol via Aerolizer has an equivalent therapeutic effect. CONCLUSION: Judged on the basis of dosing efficiency, ease of use and clinical equivalence, formoterol Aerolizer remains a useful option in the management of patients with asthma or COPD.