Treating severe asthma in the small airways: a novel inhaled dry powder formulation

Project SummaryAbstractUncontrolled inflammation in the small airways remains a major unmet need in clinical pulmonologySeverely asthmatic patients suffer from life threatening symptoms and often have exacerbations requiring costly emergency hospital treatmentsAlthough asthma patients are prescribed large numbers of inhalersthese current devices deliver very little medication into the lungsoften less thaninto small airwayswhich remain untreatedThereforewe are developing a new method of delivering medication to the small airways which will perform significantly better than current devicesWe will create a novel highly dispersible dry powder formulation containing budesonidea well studied corticosteroid medication and a hygroscopic excipientinactive ingredientresulting in an excipient enhanced growthEEGformulationThis EEG formulation will be able to uniquely treat inflammation in small airways in order to significantly reduce related symptoms of severe asthmaBy creating extra fine sizedsubmicrometerdrug powder particles combined with a hygroscopic excipientthe particles are able to avoid depositing in the mouth and throat and then will grow hygroscopically during inhalation to an optimal size to target the small airways with high depositionThe powder formulation will be delivered by a high efficiency dry powder inhaler including a novelD rod array structure that was demonstrated to best deaggregate carrier free powder formulationsThese new formulation and inhaler combinations have been shown to achieve emitted doses greater thanfine particle fractionsandltm in sizeof greater thanand initial mass median aerodynamic diametersMMADless thanmwhich result in mouth throat depositional losses of less thanThe high efficiency drug delivery will increase drug deposition in untreated lung regions and reduce systemic drug exposure compared to current devicesWe will select and evaluate two powder formulation candidates by testing their chemical stabilityphysico chemical characteristicsand aerosol performance in a realistic airway in vitro model in order to maximize the effectiveness of the formulationThis application is the first step in a translational plan to commercialize the excipient enhanced growth concept developed in the labs of DrsHindle and Longest at Virginia Commonwealth Universitysupported by Rand Rgrants from the National HeartLungand Blood InstituteNHLBIwhich has produced overpublications and two granted patentsThe translation of this technology into a clinically beneficial product will revolutionize drug delivery and symptom control by delivering medicine to currently untreated regions of the airways Project NarrativeSevere asthma is a long term debilitating and life threatening disease with no cure that remains difficult to treat using current formulations and devices because they deliver very little medication to the small airwaysThere is consensus that delivery of anti inflammatory medication to under treated small airways will have a major impact on reducing pulmonary inflammation in severe asthmatics and reducing side effects associated with undesired mouth throat depositBased on preliminary data we will develop a novel dry powder formulation and delivery method to target small airway inflammation in order to control symptoms of severe asthma