Why we need to deliver large amounts of powder to the lungs and the concurrent challenges



Pulmonary infectious diseases are difficult to treat as the incidence of drug resistance increases. Historically, therapies for Pseudomonas aeruginosa infection in Cystic Fibrosis have been treated with inhaled aerosols. Recently, non-tuberculous mycobacterial infections in a range of immunocompromised hosts, drug resistant tuberculosis and microbial infections following lung transplants have become the focus of inhaled therapy. Antimicrobial drugs are commonly low potency and require high doses to be effective. Local delivery of drug to the lungs targets local disease while minimizing systemic side effects. Dry powder inhaler (DPIs) technology has advanced significantly since the turn of the millennium making high dose delivery possible. DPIs offer the advantages of rapid bolus delivery, ease of use, storage stability and simplicity for the treatment of pulmonary infectious diseases, However, administration of high doses of dry powder presents unique challenges. At high doses efficient and reproducible delivery is a balance of mass of powder delivered on a single breath, number of breaths per dose, device, metering system and drug powder formulation. Optimization of these variables contributes to expectations of patient adherence as the daily dose escalates, especially over lengthy treatment times. To capitalize on the promise of high dose DPI therapy more research is required into the factors influencing delivery of large, tolerable drug doses and requirements of inhalers to promote patient adherence to the therapy. Recent advances in the delivery of high doses of dry powder in the context of pulmonary infectious diseases will be discussed.