Performance evaluation of nebulizers based on aerodynamic droplet diameter characterization using the Direct Laminar Incidence (DLI)
Araújo, Luciana Martins Pereira de; Abatti, Paulo José; Araújo Filho, Walter Duarte de; Alves, Rafael Fabrício
Abstract
Introduction: Optical microscope images can be useful to evaluate nebulizers considering the size of droplets produced by these devices. From this perspective, the proposed method was compared to the classic concept of Mass Median Aerodynamic Diameter (MMAD) for the ideal droplet size between 0.5-5.5 µm. Methods: We tested a sample of five home nebulizers sold on the Brazilian market. A high-speed camera coupled to a microscope obtained images of the droplets during the nebulization process, which allowed us to characterize the diameter of the aero-dispersed droplets. The Count Median Aerodynamic Diameter (CMAD) was used as measurement parameter. Results: The images obtained during the nebulization process with the five different nebulizers provided data to determine the frequency distribution of the aero-dispersed droplet population. Successive images were obtained in the range of 2.0s to evaluate the dynamic behavior of the droplets. The generated data also allowed the elaboration of histograms emphasizing the ideal diameter range of droplets between 0.5 and 5.5 μm. Conclusion: The Direct Laminar Incidence (DLI) model using digital image processing technique allowed the characterization of respirable particles. This model proposes the creation of a range of optimum absorption of the droplets by the respiratory tract. Although there is a technical limitation in the direct acquisition of images due to the depth of focus, presenting an error of 9.3%, the described method provides consistent results when compared to other droplets characterization techniques. Thus, the authors believe that Direct Laminar Incidence (DLI) is a viable method to assess the performance of nebulizers despite the requirement of adjustments and possible improvements required to minimize measurement errors.
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References
Amirav I, Newhouse MT. Deposition of small particles in the developing lung. Paediatric Respiratory Reviews. 2012; 13(2):73-8. PMid:22475251. http://dx.doi.org/10.1016/j.prrv.2011.05.006.
Boer AH, Gjaltema D, Hagedoorn P, Frinjlink HW. Characterization of inhalation aerosols: a critical evaluation of cascade impactor analysis and laser diffraction technique. International Journal of Pharmaceutics. 2002; 249(1-2):219-31. PMid:12433450. http://dx.doi.org/10.1016/S0378-5173(02)00526-4.
Chan TL, Lippmann NM. Experimental measurements and empirical modelling of the regional deposition of inhaled particles in humans. American Industrial Hygiene Association Journal. 1980; 41(6):399-409. PMid:7395753. http://dx.doi.org/10.1080/15298668091424942.
Chen S. Optimal bandwidth selection for kernel density functionals estimation. Journal of Probability and Statistics. 2015; 2015:1-21. http://dx.doi.org/10.1155/2015/242683.
Coates AL, O’Callaghan C. Drug administration by aerosol in children. In: Chernick V, Boat TF, Willmont RW, Bush A. Disorders of the respiratory tract in children. Philadelphia: Saunders-Elsevier; 2006. p. 268-79.
Coates AL, Sharon L. Drug administration by jet nebulization. Pediatric Pulmonology. 1998; 26:412-23.
Greenspan BJ. Ultrasonic and electro hydrodynamic methods for aerosol generation. In: Hickey AJ, editor. Inhalation aerosols: physical and biological basis for therapy. New York: Marcel Decker; 1996. p. 313-35.
Guyton AC, Hall JE. Textbook of medical physiology. Philadelphia, Pennsylvania: Elsevier Inc.; 2006.
Hardy JG, Newman SP, Knoch M. Lung deposition from four nebulizers. Respiratory Medicine. 1993; 87(6):461-5. PMid:8210617. http://dx.doi.org/10.1016/0954-6111(93)90074-A.
Hess DR. Nebulizers: principles and performance. Respiratory Care. 2000; 45(6):609-22. PMid:10894454.
Kwong JWT, Ho SL, Coates AL. Comparison of nebulized particle size distribution with Malvern Laser Diffraction analyzer versus Andersen Cascade Impactor and Low-Flow Marple Personal Cascade Impactor. Journal of Aerosol Medicine. 2000; 13(4):303-14. PMid:11262437. http://dx.doi.org/10.1089/jam.2000.13.303.
Mitchell JP, Nagel MW. Particle size analysis of aerosols from medicinal inhalers. Kona Powder and Particle Journal. 2004; 22:32-65. http://dx.doi.org/10.14356/kona.2004010.
Nichols SC, Brown DR, Smurthwaite M. New concept for the variable flow rate Andersen Cascade Impactor and calibration data. Journal of Aerosol Medicine. 1998; 11(Suppl 1):S133-8. PMid:10180726.
O’Callaghan C, Barry PW. The science of nebulized drug delivery. Thorax. 1997; 52(Suppl 2):S31-44. PMid:9155849. http://dx.doi.org/10.1136/thx.52.2008.S31.
Patton JS, Byron PR. Inhaling medicines: delivering drugs to the body through the lungs. Nature Reviews. Drug Discovery. 2007; 6(1):67-4. PMid:17195033. http://dx.doi.org/10.1038/nrd2153.
Siekmeier R, Scheuch G. Systemic treatment by inhalation of macromolecules – principles, problems, and examples. Journal of Physiology and Pharmacology. 2008; 59(Suppl 6):53-79. PMid:19218633.
Terzano C, Allegra L. Importance of drug delivery system in steroid aerosol therapy via nebulizer. Pulmonary Pharmacology & Therapeutics. 2002; 15(5):449-54. PMid:12406667. http://dx.doi.org/10.1006/pupt.2002.0386.
Wolters M. Methods for shape-constrained Kernel density estimation [dissertation]. London, Ontario, Canada: The University of Western Ontario; 2012.
Yang W, Peters JI, Williams RO 3rd. Inhaled nanoparticles – a current review. International Journal of Pharmaceutics. 2008; 356(1-2):239-47. PMid:18358652.
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