Lung Drug Delivery with Carbon Dioxide Aerosol Inhalers

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DESCRIPTION (provided by applicant): Asthma is one of the most common and costly illnesses in the US, with over 20 million Americans suffering from asthma with an annual societal cost of over $18 billion. Sadly, about 5000 Americans die every year from asthma, even though most asthma death is preventable with proper treatment, and the rates are especially high among the socioeconomically disadvantaged. The metered dose inhaler (MDI) is the most common form of treatment, with nearly 50 years of patient acceptance, physician confidence, and FDA approval. In the near past, MDIs used chlorofluorocarbon (CFC) propellants, but these are in the process of being phased out by the EPA and FDA due to their high ozone depletion potential (ODP). Newer MDI devices are now pressurized with hydrofluoroalkane (HFA) propellants, which overcome the ODP problem. New problems with formulations and device incompatibility made it time-consuming and expensive for the pharmaceutical industry to begin to use the new propellant HFA-134a. The new MDIs that use HFA-134a are 3-5 times more expensive than the old CFC inhalers, which is a big problem for some of the patients that need them the most, and the global warming potential is 1300 times higher for HFA-134a than for carbon dioxide. Aerophase has developed an inexpensive carbon dioxide (CO2) propellant MDI that is competitive with the HFA MDIs, with high drug delivery efficiency and dose reproducibility. We have demonstrated that asthma drugs can be effectively formulated in our compact and reliable inhalers. In our just-completed phase II SBIR project we developed inhalers using several different designs, and selected two optimized designs for SBIR Continuation testing and pilot-scale production according to the FDA Draft Guidance for Industry (Metered Dose Inhaler and Dry Powder Inhaler Drug Products: Chemistry, Manufacturing, and Controls Documentation, CDER, 10/98). Our proposed CO2 propellant MDI devices will create competition so that the entire future of the MDI is not totally dependent upon one or two HFA propellants that could develop problems with availability, affordability, long term toxicity, and/or environmental impacts. The overall mission of Aerophase Inc. is to improve healthcare through aerosol medicine. The primary purpose of the proposed project is to relieve symptoms and prevent death from asthma, especially among the hardest hit groups like African Americans, with a CO2 propellant inhaler that is as effective as and less expensive than currently available MDIs. In the US, 10% of the population has asthma, 5000 people die from it each year, and the total cost to the economy is over $18 billion per year; notably the impact of asthma is especially hard on African Americans due to a variety of factors including air quality and access to medical care. One of the most popular tools in the treatment of asthma is the metered dose inhaler (MDI), a small aerosol canister filled with drug and propellant which administers a puff of medicine for inhalation; this popular device has been used for 50 years, but is going through major changes today due to the phase-out of the use of chlorofluorocarbon propellants (because they harm the environment by damaging the protective ozone layer in the stratosphere); the most popular replacement MDI propellant has been hydrofluoroalkane (HFA), which does not harm the ozone layer; unfortunately, but not surprisingly, the prices for the new HFA inhalers are much higher than for the old inhalers, which is especially hard on socioeconomically disadvantaged patients that need asthma therapy the most. Fortunately, Aerophase has invented new, inexpensive, MDI inhalers that use carbon dioxide as the propellant gas; competition from our new inhalers-which work just as well as the HFA MDI devices in laboratory tests-will help keep asthma treatment costs down; the proposed SBIR Continuation project will allow us to make our new CO2 MDI device meet the FDA guidelines for MDI usage and stability so that we can manufacture them for human clinical testing.