SAW atomization application on inhaled pulmonary drug delivery

Pulmonary drug delivery transports the drug formulations directly to the respiratory tract in the form of inhaled particles or droplets. Because of the direct target treatment, it has significant advantages in the treatment of respiratory diseases, for example asthma. However, it is difficult to produce monodispersed particles/droplets in the 1-10 micron range, which is necessary for deposition in the targeted lung area or lower respiratory airways, in a controllable fashion. We demonstrate the use of surface acoustic waves (SAWs) as an efficient method for the generation of monodispersed micron dimension aerosols for the treatment of asthma. SAWs are ten nanometer order amplitude electroacoustic waves generated by applying an oscillating electric field to an interdigital transducer patterned on a piezoelectric substrate. The acoustic energy in the waves induces atomization of the working fluid, which contains a model drug, albuterol. Laser diffraction techniques employed to characterize the aerosols revealed mean diameter of the aerosol was around 3-4 μm. Parallel experiments employing a one-stage (glass) twin impinger as a lung model demonstrated a nearly 80% of atomized drug aerosol was deposited in the lung. The aerosol size distribution is relatively independent of the SAW frequency, which is consistent with our predictive scaling theory which accounts for the dominant balance between viscous and capillary stresses. Moreover, only 1-3 W powers consumption of SAW atomization suggests that the SAW atomizer can be miniaturized into dimensions commensurate with portable consumer devices.

[1]  B. A. Rosenberg,et al.  The use of 2-ethylhexanol in acute pulmonary edema. , 1953, Diseases of the chest.

[2]  Emmanuel P. Papadakis,et al.  Ultrasonic Instruments and Devices , 2001 .

[3]  H. Frijlink,et al.  Dry powder inhalers for pulmonary drug delivery , 2004, Expert opinion on drug delivery.

[4]  James Friend,et al.  Particle concentration and mixing in microdrops driven by focused surface acoustic waves , 2008 .

[5]  B. Marcet,et al.  General anesthetic octanol and related compounds activate wild‐type and delF508 cystic fibrosis chloride channels , 2004, British journal of pharmacology.

[6]  T. Higuchi,et al.  Characteristics of liquids atomization using surface acoustic wave , 1997, Proceedings of International Solid State Sensors and Actuators Conference (Transducers '97).

[7]  R. Llinás,et al.  The effectiveness of different isomers of octanol as blockers of harmaline-induced tremor , 1989, Pflügers Archiv.

[8]  J. Lammers,et al.  Electro-hydrodynamic atomization of drug solutions for inhalation purposes. , 2001, Journal of applied physiology.

[9]  J. M. Grace,et al.  A review of liquid atomization by electrical means , 1994 .

[10]  A. James,et al.  The distribution of eosinophils and lymphocytes in the large and small airways of asthmatics. , 1997, The European respiratory journal.

[11]  Leslie Y Yeo,et al.  Surface acoustic wave concentration of particle and bioparticle suspensions , 2007, Biomedical microdevices.

[12]  G. P. Martin,et al.  A Human Oral‐throat Cast Integrated with a Twin‐stage Impinger for Evaluation of Dry Powder Inhalers , 2000, The Journal of pharmacy and pharmacology.

[13]  Gerhard Scheuch,et al.  Clinical perspectives on pulmonary systemic and macromolecular delivery. , 2006, Advanced drug delivery reviews.

[14]  P. O'Byrne,et al.  A comparison of the efficacy and safety of inhaled corticosteroids in asthma , 1997, Allergy.

[15]  N. Thomson,et al.  Asthma : basic mechanisms and clinical management , 1988 .

[16]  Emmanuel P Papadakis Ultrasonic instruments and devices : references for modern instrumentation, techniques, and technology , 1999 .

[17]  G. Macchiarella,et al.  SAW Devices for Telecommunications: Examples and Applications , 1982 .

[18]  W. F. Miller Aerosol therapy in acute and chronic respiratory disease. , 1973, Archives of internal medicine.

[19]  James Friend,et al.  Interfacial destabilization and atomization driven by surface acoustic waves , 2008 .

[20]  Richard Dalby,et al.  Inhalation therapy: technological milestones in asthma treatment. , 2003, Advanced drug delivery reviews.

[21]  B. Dickhoff Adhesive mixtures for powder inhalation , 2006 .

[22]  H. Chrystyn Is total particle dose more important than particle distribution? , 1997, Respiratory medicine.

[23]  H. Chrystyn Is total Darticle dose more imDortant than particle , 1997 .

[24]  M. Cloupeau,et al.  ELECTROHYDRODYNAMIC SPRAYING FUNCTIONING MODES - A CRITICAL-REVIEW , 1994 .

[25]  H. Marques,et al.  Complexation of Budesonide in Cyclodextrins and Particle Aerodynamic Characterization of the Complex Solid Form for Dry Powder Inhalation , 2002 .