1703 ISSN 1756-8919 Future Med. Chem. (2011) 3(13), 1703–1718 10.4155/FMC.11.133 © 2011 Future Science Ltd Review Special F ocuS: inhalation by DeSign Chronic obstructive pulmonary disease (COPD) is the fourth largest cause of deaths worldwide and predicted to be third leading cause of death by 2030 and their associated maintenance treat- ments represent a substantial health care cost [201] . COPD is not one single disease but an umbrella term used to describe chronic lung diseases that cause limitations in lung airflow. The more familiar terms ‘chronic bronchitis’ and ‘emphy- sema’ are no longer used, but are now included within the COPD diagnosis. The most com- mon symptoms of COPD are breathlessness or a ‘need for air’, excessive sputum production and a chronic cough. However, COPD is not just sim- ply a ‘smoker’s cough’, but an underdiagnosed, life threatening lung disease that may progres- sively lead to death. COPD treatments are well established and the best outcomes are obtained by local delivery of therapeutics to the respiratory system [202] . Asthma is a similarly, and perhaps more commonly, prevalent disease, with many severely asthmatic patients presenting symptoms similar to those of COPD. Combination therapies for treatment & management of COPD & asthma Given the multicomponent nature of COPD and asthma, combining therapies with complementary modes of action provides the most effective treat- ment for the disease. Current Global Initiative for Chronic Lung Disease guidelines recom- mend a short-acting b-agonist or long-acting b-agonist (LABA) with inhaled corticosteroid (ICS) combination therapy for the management of severe and very severe COPD. This has resulted in a number of commercially available combina- tions (table 1) . In addition, combinations of a LABA with a long-acting muscarinic antagonist (LAMA) are now commercially available outside of the USA, with many new combinations cur- rently being developed (t able 2) [1,2] and emerging as promising therapeutic alternatives; for example, formoterol fumarate/glycopyrrolate [3–5] . Moreover, there is clinical evidence suggest- ing that combining all three therapies (ICS/ LABA/LAMA) can provide further clinical ben- efits and may improve quality of life because of their complementary modes of action in maintain- ing airway function [6,7] . Such evidence has been used as the basis of a triple pressurized metered dose inhaler (pMDI) combination product in a pMDI available in India (table 1) and other markets (outside of the USA, the EU and Japan). To our knowledge, there is no triple combination product in late-stage development for the USA or EU markets where the regulatory requirements tend to be more stringent. The clinical development of a dual or a triple combination for the treatment of COPD is an enormous task, as the current European and US regulations require the clinical comparison of single components, alone and co-administered sequentially, and in a combination with several doses. The clinical comparison and regulatory burden can be additionally complicated when the in vitro aerodynamic properties of the individual Novel cosuspension metered-dose inhalers for the combination therapy of chronic obstructive pulmonary disease and asthma Pressurized metered dose inhaler is the most common inhaled dosage form, ideally suited for delivering the highly potent compounds that medicinal chemists typically discover for respiratory therapeutic targets. The clinical beneft of combination therapy for asthma and chronic obstructive pulmonary disease has been well established, and many of the new discovery candidates are likely to be studied in the clinic as combination drugs even at early stages of development. We present a novel pressurized metered dose inhaler formulation approach to enable consistent aerosol performance of a respiratory therapeutic whether it is emitted from a single-, double- or triple-therapy product. This should enable rapid nonclinical and clinical assessment whether alone or in combination with other drugs, without the challenge of in vitro performance dissimilarity across product types. David Lechuga-Ballesteros †1 , Brian Noga 1 , Reinhard Vehring 1,2 , R Harris Cummings 1 & Sarvajna K Dwivedi 1 1 Pearl Therapeutics, Inc., 200 Saginaw Drive, Redwood City, CA 94063, USA 2 University of Alberta, Edmonton, AB, Canada † Author for correspondence: Tel.: +1 650 305 2607 E-mail: dlechuga@ pearltherapeutics.com For reprint orders, please contact reprints@future-science.com