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CC BY 4.0 · Pharmaceutical Fronts 2023; 05(04): e310-e320
DOI: 10.1055/s-0043-1776146
Original Article

A Technical Feasibility of Aqueous Aerosol Generation Based on the Flashing Jet: Impact of Surfactant, Electrolyte, and Drug Concentration

Qi-Wen Zheng
1   National Advance Medical Engineering Research Center, China State Institute of Pharmaceutical Industry Co., Ltd., Shanghai, People's Republic of China
,
Jian Wang
1   National Advance Medical Engineering Research Center, China State Institute of Pharmaceutical Industry Co., Ltd., Shanghai, People's Republic of China
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Abstract

This study aimed to investigate the atomization mechanism of a flashing jet (FJ), focusing on the potential factors that influence the atomization performance of the device. Those factors include surfactant, electrolyte, and drug concentration. In this work, Tween 80, sodium chloride (NaCl), and salbutamol sulfate (SBS) were used for the study. The aerosol's mass median aerodynamic diameter (MMAD) was investigated for analysis. The drug delivery ability of the FJ prototype was compared with the Pari nebulizer. Our data suggested that the MMAD of aerosol decreased as the concentration of Tween 80 increased, but the critical micelle concentration point was not influenced. Upon adding NaCl to pure water, with the increase of NaCl concentration, the MMAD of aerosol initially decreased significantly and then increased, reaching the lowest point when 0.05% NaCl was used. A higher concentration of SBS was beneficial for the atomization performance. When the SBS concentration was 5 mg/mL, the MMAD values of the FJ prototype and Pari nebulizer were 2.28 ± 0.15 and 1.03 ± 0.21 μm, respectively, and the fine particle dose (%TDD) of the FJ prototype and Pari nebulizer was 50.99 ± 5.88 and 53.51 ± 4.58%, respectively. Interestingly, the concentration of SBS has no effect on the residual dosage level of the FJ prototype, indicating that it can be applied in atomizing high-concentration solutions. In summary, surfactant, electrolyte, and drug concentration played an important role in the atomization performance of the FJ prototype and these ingredients are also crucial factors that should be considered in future formulation studies.

Keywords

inhalation drug delivery - flashing jet - inhaler prototype


Publikationsverlauf

Eingereicht: 15. Februar 2023

Angenommen: 27. September 2023

Artikel online veröffentlicht:
05. Dezember 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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  • References

  • 1 Anderson S, Atkins P, Bäckman P. et al. Inhaled medicines: past, present, and future. Pharmacol Rev 2022; 74 (01) 48-118
    CrossrefPubMedGoogle Scholar
  • 2 Laube BL. The expanding role of aerosols in systemic drug delivery, gene therapy and vaccination: an update. Transl Respir Med 2014; 2: 3
    CrossrefPubMedGoogle Scholar
  • 3 Newman SP. Drug delivery to the lungs: challenges and opportunities. Ther Deliv 2017; 8 (08) 647-661
    CrossrefPubMedGoogle Scholar
  • 4 Hickey AJ. Emerging trends in inhaled drug delivery. Adv Drug Deliv Rev 2020; 157: 63-70
    CrossrefPubMedGoogle Scholar
  • 5 McCarthy SD, González HE, Higgins BD. Future trends in nebulized therapies for pulmonary disease. J Pers Med 2020; 10 (02) 37
    CrossrefPubMedGoogle Scholar
  • 6 Geller DE. Comparing clinical features of the nebulizer, metered-dose inhaler, and dry powder inhaler. Respir Care 2005; 50 (10) 1313-1321 , discussion 1321–1322
    CrossrefPubMedGoogle Scholar
  • 7 Sher E, Bar-Kohany T, Rashkovan A. Flash-boiling atomization. Pror Energy Combust Sci 2008; 34 (04) 417-439
    CrossrefGoogle Scholar
  • 8 Bar-Kohany T, Levy M. State of the art review of flash-boiling atomization. At Sprays 2016; 26 (12) 1259-1305
    CrossrefGoogle Scholar
  • 9 Polanco G, Holdø AE, Munday G. General review of flashing jet studies. J Hazard Mater 2010; 173 (1–3): 2-18
    CrossrefPubMedGoogle Scholar
  • 10 Brown R, York JL. Sprays formed by flashing liquid Jets. AIChE J 1962; 8 (02) 149-153
    CrossrefGoogle Scholar
  • 11 Fathinia F, Al-Abdeli YM, Khiadani M. Evaporation rates and temperature distributions in fine droplet flash evaporation sprays. Int J Therm Sci 2019; 145: 106037
    CrossrefGoogle Scholar
  • 12 Cleary V, Bowen P, Witlox H. Flashing liquid jets and two-phase droplet dispersion I. Experiments for derivation of droplet atomisation correlations. J Hazard Mater 2007; 142 (03) 786-796
    CrossrefPubMedGoogle Scholar
  • 13 Jiang X, Siamas GA, Jagus K, Karayiannis KJ. Physical modelling and advanced simulations of gas–liquid two-phase jet flows in atomization and sprays. Prog Energy Combust Sci 2010; 36 (02) 131-167
    CrossrefGoogle Scholar
  • 14 Zheng QW, Yuan LJ, Wang J. A technical feasibility of aqueous aerosol generation based on the flashing jet: effects of overheat degree, jetting rate, jetting volume, and liquid type. Pharmaceutical Fronts 2023; 05 (03) e175-e186
    Artikel in Thieme ConnectGoogle Scholar
  • 15 Lobry E, Berthe JE, Spitzer D. Spray flash evaporation SFE process: identification of the driving parameters on evaporation to tune particle size and morphology. Chem Eng Sci 2021; 231: 116307
    CrossrefGoogle Scholar
  • 16 Xiong P, He S, Qiu F. et al. Experimental and mathematical study on jet atomization and flash evaporation characteristics of droplets in a depressurized environment. J Taiwan Inst Chem Eng 2021; 123: 185-198
    CrossrefGoogle Scholar
  • 17 Calay RK, Holdo AE. Modelling the dispersion of flashing jets using CFD. J Hazard Mater 2008; 154 (1–3): 1198-1209
    CrossrefPubMedGoogle Scholar
  • 18 Zhu X, Song Z, Pan X, Wang X, Jiang J. Pressure-decay and thermodynamic characteristics of subcooled liquid in the tank and their interaction with flashing jets. J Hazard Mater 2019; 378: 120578
    CrossrefPubMedGoogle Scholar
  • 19 Kitamura Y, Morimitsu H, Takahashi T. Critical Superheat for flashing of superheated liquid jets. Ind Eng Chem Fundam 1986; 25 (02) 206-211
    CrossrefGoogle Scholar
  • 20 Chen Q, Ja MK, Li Y, Chua KJ. Experimental and mathematical study of the spray flash evaporation phenomena. Appl Therm Eng 2018; 130: 598-610
    CrossrefGoogle Scholar
  • 21 Martin AR, Finlay WH. Nebulizers for drug delivery to the lungs. Expert Opin Drug Deliv 2015; 12 (06) 889-900
    CrossrefPubMedGoogle Scholar
  • 22 Harris JA, Stein SW, Myrdal PB. Evaluation of the TSI aerosol impactor 3306/3321 system using a redesigned impactor stage with solution and suspension metered-dose inhalers. AAPS PharmSciTech 2006; 7 (01) E20
    CrossrefPubMedGoogle Scholar
  • 23 Mitchell JP, Nagel MW, Wiersema KJ, Doyle CC. Aerodynamic particle size analysis of aerosols from pressurized metered-dose inhalers: comparison of Andersen 8-stage cascade impactor, next generation pharmaceutical impactor, and model 3321 Aerodynamic Particle Sizer aerosol spectrometer. AAPS PharmSciTech 2003; 4 (04) E54
    CrossrefPubMedGoogle Scholar
  • 24 Vecellio None L, Grimbert D, Bordenave J. et al. Residual gravimetric method to measure nebulizer output. J Aerosol Med 2004; 17 (01) 63-71
    CrossrefPubMedGoogle Scholar
  • 25 Tandon R, McPeck M, Smaldone GC. Measuring nebulizer output. Aerosol production vs gravimetric analysis. Chest 1997; 111 (05) 1361-1365
    CrossrefPubMedGoogle Scholar
  • 26 Wan LS, Lee PF. CMC of polysorbates. J Pharm Sci 1974; 63 (01) 136-137
    CrossrefPubMedGoogle Scholar
  • 27 Mc Callion ONM, Taylor KMG, Thomas M, Taylor AJ. The influence of surface tension on aerosols produced by medical nebulisers. Int J Pharm 1996; 129 (1–2): 123-136
    CrossrefGoogle Scholar
  • 28 Hoeve W, Gekle S, Snoeijer J. et al. Breakup of diminutive rayleigh jets. Phys Fluids 2010; 22 (12) 122003
    CrossrefGoogle Scholar
  • 29 Wang F, Fang T. Liquid jet breakup for non-circular orifices under low pressures. Int J Multiph Flow 2015; 72: 248-262
    CrossrefGoogle Scholar
  • 30 Arzhavitina A, Steckel H. Surface active drugs significantly alter the drug output rate from medical nebulizers. Int J Pharm 2010; 384 (1–2): 128-136
    CrossrefPubMedGoogle Scholar
  • 31 Dumouchel C. On the experimental investigation on primary atomization of liquid streams. Exp Fluids 2008; 45 (03) 371-422
    CrossrefGoogle Scholar
  • 32 Nozière B, Baduel C, Jaffrezo JL. The dynamic surface tension of atmospheric aerosol surfactants reveals new aspects of cloud activation. Nat Commun 2014; 5 (01) 3335
    CrossrefPubMedGoogle Scholar
  • 33 Eastoe J, Dalton JS. Dynamic surface tension and adsorption mechanisms of surfactants at the air-water interface. Adv Colloid Interface Sci 2000; 85 (2–3): 103-144
    CrossrefPubMedGoogle Scholar
  • 34 Qazi MJ, Schlegel SJ, Backus EHG, Bonn M, Bonn D, Shahidzadeh N. Dynamic surface tension of surfactants in the presence of high salt concentrations. Langmuir 2020; 36 (27) 7956-7964
    CrossrefPubMedGoogle Scholar
  • 35 Tripathi MK, Sahu KC, Govindarajan R. Dynamics of an initially spherical bubble rising in quiescent liquid. Nat Commun 2015; 6: 6268
    CrossrefPubMedGoogle Scholar
  • 36 Beck-Broichsitter M, Oesterheld N. Electrolyte type and nozzle composition affect the process of vibrating-membrane nebulization. Eur J Pharm Biopharm 2017; 119: 11-16
    CrossrefPubMedGoogle Scholar
  • 37 Oatley-Radcliffe DL, Aljohani N, Williams PM, Hilal N. Chapter 18 - Electrokinetic phenomena for membrane charge. In: Hilal N, Ismail AF, Matsuura T, Oatley-Radcliffe D. 1st ed.. Membrane Characterization. Elsevier Inc.; 2017: 405-422
    Google Scholar
  • 38 Holbrook L, Hindle M, Longest PW. Generating charged pharmaceutical aerosols intended to improve targeted drug delivery in ventilated infants. J Aerosol Sci 2015; 88: 35-47
    CrossrefPubMedGoogle Scholar
  • 39 Lv C, Tsona NT, Du L. Sea spray aerosol formation: results on the role of different parameters and organic concentrations from bubble bursting experiments. Chemosphere 2020; 252: 126456
    CrossrefPubMedGoogle Scholar
  • 40 Mueannoom W, Srisongphan A, Taylor KM, Hauschild S, Gaisford S. Thermal ink-jet spray freeze-drying for preparation of excipient-free salbutamol sulphate for inhalation. Eur J Pharm Biopharm 2012; 80 (01) 149-155
    CrossrefPubMedGoogle Scholar
  • 41 Beck-Broichsitter M, Prüfer N, Oesterheld N, Seeger W, Schmehl T. Nebulization of active pharmaceutical ingredients with the eFlow(®) rapid: impact of formulation variables on aerodynamic characteristics. J Pharm Sci 2014; 103 (08) 2585-2589
    CrossrefPubMedGoogle Scholar
  • 42 Tjahjadi M, Stone H, Ottino J. Satellite and subsatellite formation in capillary breakup. J Fluid Mech 1992; 243: 297-317
    CrossrefGoogle Scholar
  • 43 Rajagopal K, Jayabalakrishnan SS. Volumetric, ultrasonic speed, and viscometric studies of salbutamol sulphate in aqueous methanol solution at different temperatures. J Chem Thermodyn 2010; 42 (08) 984-993
    CrossrefGoogle Scholar