Aerosol generation using an integrated control and dispersion mechanism based on powder flow characteristics

The production of an aerosol by a dry powder inhaler (DPI) requires dispersion of drug particles, a process highly dependent upon the formulation and upon energy provided by the patient's inhalation. It is proposed that measurements of the flow properties of powders can be used to derive signals that will control dispersion and reduce these dependencies in an active DPI. Specific aims addressing this hypothesis include: the measurement of flow properties of powders; the development of an active mechanism of dispersion; the derivation of signals for dispersion; and the development of a dispersion model and control algorithm.;Instrumentation and analysis of vibrating spatula and rotating drum methods of powder characterization was improved, characterized and utilized for powder flow analysis. The vibrating spatula differentiated the flow properties of lactose and maltodextrin excipients and the rotating drum was used to provide a basis for the derivation of signals used to disperse these powders in model albuterol sulfate containing formulations. A vibration membrane for the production of dispersion signals was constructed from a piezoelectric polymer, polyvinyidene difluoride, and mounted in a dispersion tube. In vitro testing of the dispersion properties of the device showed an increase of emitted dose (ED) from 57% and 65% for no signal and a sine wave signal to 81% for the derived signal using the lactose formulation. The fine particle fraction (FPF) increased from 9% to 13% with respect to the nominal dose. The fine particle mass (FPM) increased from 37 mug to 52 mug for a 400 mug nominal dose. For the maltodextrin formulation, the ED and FPF increased from 39% to 95% and 3.6% to 8.1%, respectively. A shear force fluidization model was derived and the flow rate dependence used in the calculation of membership functions in a fuzzy logic dispersion control algorithm. The control algorithm correctly predicted the trend in vibration amplitude needed to produce a uniform FPF.;A novel dispersion mechanism utilized fundamental knowledge of powder flow to improve dispersion in a DPI prototype. The control algorithm is the first proposed for the active control of DPI dispersion.