NEBULIZERS: AERODYNAMIC DROPLET DIAMETER CHARACTERIZATION AND PHYSICOCHEMICAL PROPERTIES OF DRUGS TO TREAT SEVERE ACUTE RESPIRATORY SYNDROME CORONA VIRUS 2 (SARS-COV-2)
DOI:
https://doi.org/10.29121/granthaalayah.v8.i7.2020.420Keywords:
Drugs, SARS-Cov-2, Nebulizers, Direct Laminar Incidence, Physicochemical PropertiesAbstract [English]
Currently, several drugs are being used systemically to treat Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). However, few studies discuss the possibility of using the inhalation route for this treatment. Pneumatic and ultrasonic nebulizers are increasingly used due to the ease with which these media deliver drugs through an aerosol suspension to deliver drugs in a localized manner in the respiratory tract, providing greater efficiency of absorption. This study aims to characterize the droplet diameters by bands of "breathable particles" generated by nebulizers commercialized in Brazil (2 pneumatic and 1 ultrasonic), using the direct laminar incidence (DLI) technique. In addition, to discuss the use of drugs by inhalation based on the physicochemical and pharmacology properties. In the nebulization procedure, the images of the dispersed aero droplets were captured using the DLI technique. Droplet diameter distribution histograms were elaborated, emphasizing the range of droplets with diameters between 1.0 to 5.0 µm. The results attested that each nebulizer has its own characteristic of delivering the aerodynamic suspension in the nebulization process. In this study, DLI represents a viable alternative for characterization of the aero dispersed droplets, of drugs used worldwide to treat SARS-CoV-2 signs and symptoms.
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References
Kiselev, D., Matsvay, A., Abramov. I., Dedkov, V., Shipulin, G. and Khafizov, K. Current Trends in Diagnostics of Viral Infections of Unknown Etiology, Viruses. 12, 2020, 211. DOI: https://doi.org/10.3390/v12020211
Woolhouse, M., Scott, F., Hudson, Z., Howey, R. and Chase-Topping, M. Human viruses: Discovery and emergence, Philosophical Transactions of the Royal Society B: Biological Sciences. 367, 2012, 2864–2871. DOI: https://doi.org/10.1098/rstb.2011.0354
Hasan, S., Ahmad,S. A., Masood, R. and Saeed, S. Ebola virus: A global public health menace: A narrative review, Journal of Family Medicine and Primary Care. 8, 2019, 2189–2201. DOI: https://doi.org/10.4103/jfmpc.jfmpc_297_19
Kazmi, S. S., Ali, W., Bibi, N. and Nouroz, F. A review on Zika virus outbreak, epidemiology, transmission and infection dynamics, Journal of Biological Research-Thessaloniki. 27, 2020, 5. DOI: https://doi.org/10.1186/s40709-020-00115-4
McBride1, R. and Fielding, B.C. The Role of Severe Acute Respiratory Syndrome (SARS)-Coronavirus Accessory Proteins in Virus Pathogenesis, Viruses. 4, 2012, 2902–2923. DOI: https://doi.org/10.3390/v4112902
Astuti, I. and Ysrafil. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response, Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 14, 2020, 407–412. DOI: https://doi.org/10.1016/j.dsx.2020.04.020
Mangal, S., Nie, H., Xu, R.,Guo, R., Cavallaro, A., Zemlyanov, D. and Zhou, Q. Physico-Chemical Properties, Aerosolization and Dissolution of Co-Spray Dried Azithromycin Particles with L-Leucine for Inhalation, Pharmaceutical Research. 8, 2018, 28. DOI: https://doi.org/10.1007/s11095-017-2334-9
Ibrahim, M., Verma, R. and Garcia-Contreras, L. Inhalation drug delivery devices: technology update, Medical devices (Auckland, N.Z.). 8, 2015, 131–139. DOI: https://doi.org/10.2147/MDER.S48888
Tsuda, A., Henry, F. S. and Butler, J. P. Particle transport and deposition: basic physics of particle kinetics, Comprehensive Physiology. 3, 2013, 1437–1471. DOI: https://doi.org/10.1002/cphy.c100085
Anderson, P. J. History of Aerosol Therapy: Liquid Nebulization to MDIs to DPIs, Respiratory Care. 50, 2005, 1139–1150.
Ari, A., Hess, D., Myers, T. R. and Rau, J. L. A guide to aerosol delivery devices for respiratory therapists. 2nd. Dallas, Texas: American Association for Respiratory Care, 2009.
Amirav, I., Balanov, I., Gorenberg, M., Groshar, D. and Luder, A. S. Nebulizer hood compared to mask in wheezy infants: aerosol therapy without tears!, Archives of Disease in Childhood. 88, 2003, 719-723. DOI: https://doi.org/10.1136/adc.88.8.719
Tena, A. F., Clarà, P. C. Deposition of Inhaled Particles in the Lungs, Archivos de Bronconeumología. 48, 2012, 240–246. DOI: https://doi.org/10.1016/j.arbr.2012.02.006
Carvalho, T. C., Peters, J. I. and Williams 3rd, R. O. Influence of particle size on regional lung deposition – What evidence is there? International Journal of Pharmaceutics. 406, 2011, 1–10. DOI: https://doi.org/10.1016/j.ijpharm.2010.12.040
Willeke, K. and Baron, P. A. Aerosol Measurement - Principles, Techniques and Applications: An Nostrand Reinhold, New York, 1993.
Ho, K. K. L., Kellaway, I.W. and Tredree, R. L. Particle size analysis of nebulized aerosols using Fraunhofer laser diffraction and inertial impaction methods, Journal of Pharmacy and Pharmacology. 38, 1986, S26P. DOI: https://doi.org/10.1111/j.2042-7158.1986.tb14255.x
Patton, J. S. and Byron, P. R. Inhaling medicines: delivering drugs to the body through the lungs, Nature Reviews Drug Discovery. 6, 2007, 67–74. DOI: https://doi.org/10.1038/nrd2153
Bennet, W. D. Aerosolized drug delivery: fractional deposition of inhaled particles, Journal of Aerosol Medicine. 4, 1991, 223–227. DOI: https://doi.org/10.1089/jam.1991.4.223
Allen T. Powder Sampling and Particle Size Determination, Elsevier Press, Amsterdam, Netherland. 2003. DOI: https://doi.org/10.1016/B978-044451564-3/50003-6
Yeo, L. Y., Friend, J. R., McIntosh, M. P., Meeusen, E. N. T. and Morton, D. A. V. Ultrasonic nebulization platforms for pulmonary drug delivery, Expert Opinion on Drug Delivery. 7, 2010, 663–679. DOI: https://doi.org/10.1517/17425247.2010.485608
Dolovich, M. Measurement of particle size characteristics of metered dose inhalers (MDI)aerosols, Journal of Aerosol Medicine. 4, 1991, 251–263. DOI: https://doi.org/10.1089/jam.1991.4.251
Porstendörfe, J., Gebhart, J. and Riöbig, G. Effect of Evaporation on the Size Distribution of Nebulized Aerosols, Journal of Aerosol Science. 8, 1977, 371–380. DOI: https://doi.org/10.1016/0021-8502(77)90031-3
Dolovich, M. B. and Dhand. R. Aerosol drug delivery: developments in device design and clinical use, Lancet. 377, 2011, 1032–1045. DOI: https://doi.org/10.1016/S0140-6736(10)60926-9
Kippax, P. Measuring Particle Size Using Modern Laser Diffraction Techniques, Paint & Coatings Industry Magazine. 21, 2005, 42–47.
Araújo, L. M. P., Abatti, P. J., Araújo Filho, W. D. and Alves, R. F. Performance evaluation of nebulizers based on aerodynamic droplet diameter characterization using the Direct Laminar Incidence (DLI), Research on Biomedical Engineering. 33, 2017, 105–112. DOI: https://doi.org/10.1590/2446-4740.05316
O’Callaghan, C. and Barry, P. W. The science of nebulised drug delivery, Thorax. 52, 1997, 31–44. DOI: https://doi.org/10.1136/thx.52.2008.S31
De Boer, A. H., Gjaltema, D., Hagedoorn, P. and Frijlink, H. W. Characterization of inhalation aerosols: a critical evaluation of cascade impactor analysis and laser diffraction technique, International Journal of Pharmaceutics. 249, 2002, 219–231. DOI: https://doi.org/10.1016/S0378-5173(02)00526-4
Durst F., Melling, A. and Whitelaw, J. H. Principles and practice of laser-Doppler anemometry, Academic Press, 1981.
Zhou, H., Wu, J. and Zhang, J. Digital Image Processing: Part I. Bookboon, 2010.
Soille, P. Morphological Image Analysis: Principles and Applications, Springer-Verlag, 1999. DOI: https://doi.org/10.1007/978-3-662-03939-7
Gonzalez, R. C. and Woods, R. E. Digital Image Processing, Prentice-Hall, Upper Saddle River, NJ, 2002.
PUBCHEM, United States of America. (2020). Retrieved from: https://pubchem.ncbi.nlm.nih.gov/compound.
DRUG BANK, Canadá. (2020). Retrieved from: https://www.drugbank.ca/drugs.
Brazilian Pharmacopeia, 6th ed.; Brasília: Brazilian Health Surveillance Agency; 2019.
Ministry of Health, Brazilian Health Surveillance Agency (ANVISA). Normative Instruction No. 33. Brasília. (2019). Retrieved from: http://portal.anvisa.gov.br/documents/10181/3178137/IN_33_2019_.pdf/bf52c1a2-aa89-4b94-9001-98c457777e93.
Ministry of Health, Brazilian Health Surveillance Agency (ANVISA). Resolution of the Board of Directors – RDC No. 278. Brasília. (2019). Retrieved from: http://portal.anvisa.gov.br/documents/10181/3178137/RDC_278_2019_.pdf/69422274-3489-44b9-83d8-88b2044cc147.
Mansour, H. M. Inhaled medical aerosols by nebulizer delivery in pulmonary hypertension, Pulmonary Circulation. 8, 2018, 2045894018809084. DOI: https://doi.org/10.1177/2045894018809084
Borghardt, J. M., Kloft, C. and Sharma, A. Inhaled Therapy in Respiratory Disease: The Complex Interplay of Pulmonary Kinetic Processes, Canadian Respiratory Journal. 2018, 2018, 2732017.
Zhang, Y., Geng, X., Tan, Y., Li, Q., Xu, C., Xu, J., Hao, L., Zeng, Z., Luo, X., Liu, F. and Wanga, H. New understanding of the damage of SARS-CoV-2 infection outside the respiratory system, Biomedicine & Pharmacotherapy. 127, 2020, 110195. DOI: https://doi.org/10.1016/j.biopha.2020.110195
Alper, J. D. and Gertner, E. Off‐Label Therapies for COVID‐19—Are We All In This Together?, Clinical Pharmacology & Therapeutics. 2020, 10.1002/cpt.1862. “in press.” DOI: https://doi.org/10.1002/cpt.1862
Romani, L., Tomino, C., Puccetti, P. and Garaci, E. Off-label therapy targeting pathogenic inflammation in COVID-19, Cell Death Discovery. 6, 2020, 49. DOI: https://doi.org/10.1038/s41420-020-0283-2
Pramod, K., Tahir, M. A., Charoo, N. A., Ansari, S. H. and Ali, J. Pharmaceutical product development: A quality by design approach. International Journal of Pharmaceutical Investigation. 6, 2016, 129–138. DOI: https://doi.org/10.4103/2230-973X.187350
Bannan, C. C., Calabró, G., Kyu, D. Y. and Mobley, D. L. Calculating partition coefficients of small molecules in octanol/water and cyclohexane/water, Journal of Chemical Theory and Computation. 12, 2016, 4015–4024. DOI: https://doi.org/10.1021/acs.jctc.6b00449
Sangster, J. J. Octanol‐Water Partition Coefficients of Simple Organic Compounds, Journal of Physical and Chemical Reference Data. 18, 1989, 1111–1227. DOI: https://doi.org/10.1063/1.555833
Labiris, N. R. and Dolovich, M. B. Pulmonary drug delivery. Part II: The role of inhalant delivery devices and drug formulations in therapeutic effectiveness of aerosolized medications, British Journal of Clinical Pharmacology. 56, 2003, 600–612. DOI: https://doi.org/10.1046/j.1365-2125.2003.01893.x
Chorepsima, S., Kechagias, K. S., Kalimeris, G., Triarides, N. A. and Falagas, M. E. Spotlight on inhaled ciprofloxacin and its potential in the treatment of non-cystic fibrosis bronchiectasis, Drug Design, Development and Therapy. 12, 2018, 4059–4066. DOI: https://doi.org/10.2147/DDDT.S168014
Bai, S.; Thomas, C.; Ahsan, F. Dendrimers as a carrier for pulmonary delivery of enoxaparin, a low-molecular weight heparin. Journal of Pharmaceutical Sciences. 96, 2007, 2090–2106. DOI: https://doi.org/10.1002/jps.20849
Daley-Yates, P. T. Inhaled corticosteroids: potency, dose equivalence and therapeutic index, British Journal of Clinical Pharmacology. 80, 2015, 372–380. DOI: https://doi.org/10.1111/bcp.12637
Dumont, E. F., Oliver, A. J., Ioannou, C., Billiard, J., Dennison, J., Van den Berg, F., Yang, S., Chandrasekaran, V., Young, G. C., Lahiry, A., Starbuck, D. C., Harrell, A. W., Georgiou, A., Hopchet, N., Gillies, A. and Baker, S. J. A Novel Inhaled Dry-Powder Formulation of Ribavirin Allows for Efficient Lung Delivery in Healthy Participants and Those with Chronic Obstructive Pulmonary Disease in a Phase 1 Study. Antimicrobial Agents and Chemotherapy. 64, 2020, e02267-19. DOI: https://doi.org/10.1128/AAC.02267-19
Anekthananon, T., Pukritayakamee, S., Ratanasuwan, W., Jittamala, P., Werarak, P., Charunwatthana, P., Suwanagool, S., Lawpoolsri, S., Stepniewska, K., Sapchookul, P., Puthavathana, P., Fukuda, C., Lindegardh, N., Tarning, J., White, N. J., Day, N. and Taylor, W. R. J. Oseltamivir and inhaled zanamivir as influenza prophylaxis in Thai health workers: a randomized, double-blind, placebo-controlled safety trial over 16 weeks, Journal of Antimicrobial Chemotherapy. 68, 2013, 697–707. DOI: https://doi.org/10.1093/jac/dks418
Leyva-Gradoa, V. H. Palese, P. Aerosol administration increases the efficacy of oseltamivir for the treatment of mice infected with influenza viruses, Antiviral Research. 142, 2017, 12–15. DOI: https://doi.org/10.1016/j.antiviral.2017.03.002
Rossignol, J. F. Nitazoxanide, a new drug candidate for the treatment of Middle East respiratory syndrome coronavirus, Journal of Infection and Public Health. 9, 2016, 227–230. DOI: https://doi.org/10.1016/j.jiph.2016.04.001
Klimke, A., Hefner, G., Will, B. and Vossa, U. Hydroxychloroquine as an aerosol might markedly reduce and even prevent severe clinical symptoms after SARS-CoV-2 infection, Medical Hypotheses. 142, 2020, 109783. DOI: https://doi.org/10.1016/j.mehy.2020.109783
Sun, D. Remdesivir for Treatment of COVID-19: Combination of Pulmonary and IV Administration May Offer Aditional Benefit, The AAPS Journal. 22, 2020, 77. DOI: https://doi.org/10.1208/s12248-020-00459-8
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