Vibration Technology for Active Dry-Powder Inhalers

Timothy M. Crowder, PhD, is chief technology officer at Oriel Therapeutics, Inc., PO Box 14087, Research Triangle Park, NC 27709, tel. 919.313.1290 ext. 11, fax 919.313.1295, [email protected]. ctive dry-powder inhalers (DPIs) for pulmonary drug delivery have been under development for at least 10 years, but to date no such device has been approved by FDA. Like propellant-driven metered-dose inhalers, active devices use a source external to the patient to provide the energy needed for powder dispersion. To generate an aerosol, powder in a static state must be fluidized and entrained into the patient’s inspiratory airflow. Fluidization and entrainment require the input of energy to the static powder bed. One well-known mechanism for providing energy to powder is vibration. Powder flow under vibration is inherently nonlinear, but an understanding of its nonlinear characteristics may offer a means to linearize the flow. Linearized flow, in turn, may decrease variability in the dispersion of fluidized powders. In addition, a sound scientific understanding of powder flow and dispersion offers an opportunity to eliminate the need for reformulation. A new approach under development entails the calculation of nonlinear vibration signals (frequencies) from a fundamental physical characterization of powder flow that allows the signals to be translated into the necessary vibratory energy. These frequencies are applied to the powder by an actuator incorporated into the packaging material. Data generated by the use of the new technology in a wide range of pharmaceutically relevant powders have demonstrated highly reproducible dosing.