Overcoming Dose Limitations Using the Orbital® Multi-Breath Dry Powder Inhaler

Abstract

A new approach to delivering high doses of dry powder medicaments to the lung is presented. The Orbital(®) dry powder device is designed to deliver high doses of drugs to the respiratory tract in a single dosing unit, via multiple inhalation maneuvers, overcoming the need to prime or insert multiple capsules. The Orbital was tested in its prototype configuration and compared with a conventional RS01 capsule device. Three formulations were evaluated: 200 mg of spray-dried ciprofloxacin formulation for respiratory infection, 200 mg of spray-dried mannitol formulation for mucus clearance, and 100, 200, and 400 mg of co-spray-dried 1:8 formulations containing ciprofloxacin and mannitol as combination therapy. The systems were evaluated in terms of physicochemical properties and tested using a multistage liquid impinger at 60 L/min. Emptying rates were evaluated, and the aerosolization performance compared with 10 capsules used sequentially in the RS01. The systems were different in terms of morphology, thermal response, moisture sorption, and stability; however, they had similar sizes when measured by laser diffraction, making them suitable for comparison in the Orbital and RS01 devices. The aerosolization performance from the Orbital device and RS01 was dependent on the formulation type; however, the fine particle fraction (FPF) produced by the Orbital device was higher than that by the RS01. The FPFs for ciprofloxacin, mannitol, and co-spray-dried formulation were 67.1±1.8, 47.1±2.2, and 42.0±1.8, respectively. For the Orbital, 90% of the loaded dose was delivered within 10 inhalation maneuvers, with the profile being dependent on the formulation type. The Orbital provides a means of delivering high doses of medicine to the respiratory tract through multiple breath maneuvers after a single actuation. This approach will allow the delivery of a wide range of high-payload formulations (>100 mg) for the treatment of a variety of lung disorders. To date, no such passive device exists that meets these crucial criteria.