Research Article The Delivery of High-Dose Dry Powder Antibiotics by a Low-Cost Generic Inhaler Thaigarajan Parumasivam, 1 Sharon S. Y. Leung, 1 Patricia Tang, 1 Citterio Mauro, 2 Warwick Britton, 3,4 and Hak-Kim Chan 1,5 Received 27 May 2016; accepted 9 September 2016 Abstract. The routine of loading multiple capsules for delivery of high-dose antibiotics is time consuming, which may reduce patient adherence to inhaled treatment. To overcome this limitation, an investigation was carried out using four modified versions of the Aerolizer® that accommodate a size 0 capsule for delivery of high payload formulations. In some prototypes, four piercing pins of 0.6 mm each were replaced with a single centrally located 1.2-mm pin and one-third reduced air inlet of the original design. The performance of these inhalers was evaluated using spray-dried antibiotic powders with distinct morphologies: spherical particles with a highly corrugated surface (colistin and tobramycin) and needle-like particles (rifapentine). The inhalers were tested at capsule loadings of 50 mg (colistin), 30 mg (rifapentine) and 100 mg (tobramycin) using a multistage liquid impinger (MSLI) operating at 60 L/min. The device with a single pin and reduced air inlet showed a superior performance than the other prototypes in dispersing colistin and rifapentine powders, with a fine particle fraction (FPF wt% <5 μm in the aerosol) between 62 and 68%. Subsequently, an Aerolizer® with the same configuration (single pin and one-third air inlet) that accommo- dates a size 00 capsule was designed to increase the payload of colistin and rifapentine. The performance of the device at various inspiratory flow rates and air volumes achievable by most cystic fibrosis (CF) patients was examined at the maximum capsule loading of 100 mg. The device showed optimal performance at 45 L/min with an air volume of 1.5–2.0 L for colistin and 60 L/min with an air volume of 2.0 L for rifapentine. In conclusion, the modified size 00 Aerolizer® inhaler as a low-cost generic device demonstrated promising results for delivery of various high-dose formulations for treatment of lung infections. KEY WORDS: aerosolisation; dry powder inhaler; high-dose delivery; lung infection; modified Aerolizer®. INTRODUCTION Over the last two decades, pulmonary drug delivery has gained considerable interest as a promising alternative to conven- tional routes of drug administration for the treatment of various chronic pulmonary diseases, including asthma, cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) (1–3). Nebulisers are the cornerstone of inhalation therapy, which can deliver large dosages, but they are time-consuming to use, generally bulky and expensive and cause a large amount of drug wastage during continuous operation (4). The pressurised metered dose inhaler (pMDI) is compact, portable and optimal for small doses (maximum dose 5 mg) and can be used quickly (5). However, delivery ef ficiency of pMDI depends on the patient’s breathing pattern and hand-mouth coordination (4). The device has also suffered a phase out of chlorofluorocarbon (CFC) and dif ficulties with the new hydrofluoroalkane (HFA) reformulations (6). The dry powder inhaler (DPI) is a passive device, known for its convenient use and high lung deposition, and does not require a strict hand-mouth coordination (4). Because of these advantages, the DPI has garnered significant attention from researchers and pharmaceutical companies, and this is reflected by a plethora of dry powder-based commercial products and clinical trials (7–9). Electronic supplementary material The online version of this article (doi:10.1208/s12248-016-9988-9) contains supplementary material, which is available to authorized users. 1 Advanced Drug Delivery Group, Faculty of Pharmacy, The University of Sydney, Sydney, NSW 2006, Australia. 2 R & D and Industrialization, Plastiape S.p.A., 23875, Osnago, Italy. 3 Tuberculosis Research Program, Centenary Institute, The Univer- sity of Sydney, Sydney, NSW 2006, Australia. 4 Infectious Diseases and Immunology, Sydney Medical School, The University of Sydney, Sydney, NSW 2006, Australia. 5 To whom correspondence should be addressed. (e-mail: kim.chan@sydney.edu.au) The AAPS Journal ( # 2016) DOI: 10.1208/s12248-016-9988-9 1550-7416/16/0000-0001/0 # 2016 American Association of Pharmaceutical Scientists