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Silicon-based MHz Multiple Fourier-Horn Ultrasonic Nozzles for Pulmonary Drug Delivery

  • Author(s): LIN, SHIH-KAI
  • Advisor(s): Tsai, Chen S
  • et al.
Abstract

Medicinal particles or aerosols of the size range from 1 to 5 µm at high output rates are required for efficient and effective inhaled drug delivery to rapidly administer a large dose of medicine to the lung. Current commercial devices all suffer from broad aerosol size distributions, with a geometrical standard deviation (GSD) range of 1.5 to >4.0, making it difficult to deliver sufficient drug to targeted sites precisely and rapidly. The silicon-based megahertz multiple-Fourier horn ultrasonic nozzles (MFHUNs) presented in this dissertation have been shown capable of producing such micrometer-sized particles (aerosols) at high output rate and low electrical drive power. The precise control of aerosol size and much narrower size distribution achieved by the new device will greatly improve targeting of treatment within the respiratory tract and improve delivery efficiency, resulting in better efficacy, fewer side effects, shorter treatment times, and lower medication costs compared with the existing nebulizers. The basic ultrasonic nozzle consists of a drive section and a resonator section with a lead zirconate titanate (PZT) transducer bonded on the drive section to excite large mechanical vibrations on the end face of the distal horn to initiate instability of megahertz (MHz) Faraday waves on the free liquid surface. In operation, a medicinal liquid layer with a certain thickness is formed on the end face of the nozzle tip via a silica tube. The dramatic resonance effect among the multiple Fourier horns and high growth rate of the MHz Faraday waves excited on the medicinal liquid layer together facilitate ejection of monodisperse aerosols of desirable size range (2-5 µm) at low electrical power(<1.0W). The interaction between the medicinal liquid layer and the MFHUN was studied for optimization of nozzle designs. The effect of variations of the medicinal liquid layer on the performance of MFHUN was minimized by increasing the half-power bandwidth of the MFHUN. The temporal instability of Faraday waves has been observed and studied on both a planar liquid layer and a spherical water drop. The critical excitation displacement of the nozzle end face for temporal instability of MHz Faraday waves on the liquid layer was verified via measuring the threshold drive voltage. The theoretical prediction of the aerosol diameter was verified by the size analyses of aerosols produced at the drive frequencies of 1.0, 1.5 2.0 and 2.5 MHz. A number of common pulmonary drugs have been nebulized with desirable aerosol sizes and output rates using the pocket-size units consisting of a single nozzle or twin nozzles. A versatile ultrasonic nebulizer that utilizes a twin-nozzle of multiple Fourier horns at 1-2 MHz drive frequencies has also been realized to demonstrate the capability of doubling the aerosol output rate of the same drug solution as well as simultaneous aerosolization of two different drug solutions.

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