Skip to main content
SpringerLink
Log in

A review of the technical aspects of drug nebulization

  • Published:
Pharmacy World & Science Aims and scope Submit manuscript

Abstract

Nebulizers are widely used for the inhalation of drug solutions in a variety of respiratory diseases. The efficacy of nebulizer therapy is influenced by a great number of factors, including the design of the device and the characteristics of the drug solution. Incorrect cleaning, maintenance and disinfection procedures may change the nebulizer performance in time, whereas patient factors can influence the lung deposition of the generated aerosol. In this review the technical aspects of nebulization of drug solutions will be discussed. Two main parameters are generally used to evaluate the performance of nebulizers: the droplet size distribution of the aerosol and the drug output rate. The droplet size distribution and the drug output rate are basically determined by the design and user conditions of the nebulizer. A higher gas flow of the compressor in a jet nebulizer or a higher vibration frequency of the piezo electric crystal in an ultrasonic nebulizer, decreases the droplet size. The choice of the type of nebulizer for nebulization of a certain drug solution may initially be based on laboratory evaluation. The major part of the mass or volume distribution should preferably correspond with aerodynamic particle diameters in the range of 1 to 5 micrometer. The intended drug output must be realized within a reasonable nebulization time (less than 30 min). From the drug output only a minor fraction will be deposited in the lung. The relation between in vitro and in vivo deposition is only partly understood and to date it has not been possible to predict drug delivery only from in vitro studies on nebulizers. Therefore, studies in patients should be performed before a drug solution for nebulization can be recommended for clinical practice. The mechanical properties of nebulizers are likely to change during use. An average utilization time of nebulizers is not available. Therefore, the performance of nebulizers should be checked periodically. Patient compliance in nebulizer therapy is relatively low. This is partly due to the fact that, at present, drug solutions for nebulizers cannot be administered efficiently within a short period of time. More efficient systems should be developed. If possible, nebulizers should be substituted to more efficient systems, e.g. dry powder inhalers or metered dose inhalers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  1. Newman SP, Clarke SW. Therapeutic aerosols. 1. Physical and practical considerations. Thorax 1983;38:881-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Le Souëf. Meeting introduction. Eur Respir Rev 1997,7:375.

    Google Scholar 

  3. Mukhopadhyay S, Singh M, Cater JI, Ogston S, Franklin M, Olver RE. Nebulised antipseudomonal antibiotic therapy in cystic fibrosis: a meta-analysis of benefits and risks. Thorax 1996;51:364-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Touw DJ, Brimicombe RW, Hodson ME, Heijerman HGM, Bakker W. Inhalation of antibiotics in cystic fibrosis. Eur Respir J 1995;8:1594-1604.

    CAS  PubMed  Google Scholar 

  5. Deenstra M. De inhalatie als toedieningsvorm van geneesmiddelen. GeBu 1992,10:44-7.

    Google Scholar 

  6. Kendrick AH, Smith EC, Denyer J. Nebulizers-fill volume, residual volume and matching of nebulizers to compressor. Resp Med 1995;89:157-9.

    Article  CAS  Google Scholar 

  7. Pedersen S. Inhalers and nebulizers: which to choose and why. Resp Med 1996;90:69-77.

    Article  CAS  Google Scholar 

  8. Newman SP. In: Draco AB (Ed.), Nebulizer therapy: scientific and technical aspects. Lund, Sweden, 1989:1-38.

  9. Loffert DT, Ikle D, Nelson HS. A comparison of commercial jet nebulizers. Chest 1994; 106; 1788-92.

    Article  CAS  PubMed  Google Scholar 

  10. McCallion ONM, Taylor KMG, Bridges PA, Thomas M, Taylor AJ. Jet nebulizers for pulmonary delivery. Int J Pharm 1996;130:1-11.

    Article  CAS  Google Scholar 

  11. Kisch GL, Paloucek FP. Metered-dose inhalers and nebulizers in the acute setting. Ann Pharmacother 1992;26:92-5.

    Article  CAS  PubMed  Google Scholar 

  12. De Boer AH, Bolhuis GK, Gjaltema D, Hagedoorn P. Inhalation chracteristics and their effects on in vitro drug delivery from dry powder inhalers. Part 3: the effect of flow increase rate (FIR) on the in vitro drug release from the Pulimicort 200 Turbuhaler. Int J Pharm 1997;153:67-77.

    Article  CAS  Google Scholar 

  13. Selroos O, Pietinalho A, Riska H. Delivery devices for inhaled asthma medication. Clin Immunother 1996;6:273-99.

    Article  Google Scholar 

  14. Newman SP, Pavia D. Aerosol deposition in man. In: Moren F, Newhouse MT, Dolovich MB, ed. Aerosols in medicine. Amsterdam Elsevier 1985 193-218.

    Google Scholar 

  15. Wolff RK, Niven RW. Generation of aerosolized drugs. J aerosol Med 1994; 7: 89-106.

    Article  CAS  PubMed  Google Scholar 

  16. O'Callaghan C, Barry PW. The science of nebulised drug delivery. Thorax 1997, 52 (Suppl 2),S31-S44.

    Article  PubMed  PubMed Central  Google Scholar 

  17. British Thoracic society Nebuliser project Group. Thorax 1997;52 (suppl 2):S1.

    Google Scholar 

  18. Le souef P. The meaning of the lung dose. Allergy 1999; 54 (Suppl 49):93-6.

    Article  PubMed  Google Scholar 

  19. Smith EC, Denyer J, Kendrick AH. Comparison of twenty three nebulizer/compressor combinations for domiciliary use. Eur Respir J 1995;7:1214-21.

    Article  Google Scholar 

  20. Le Brun PPH, de Boer AH, Gjaltema D, Hagedoorn P, Heijerman HGM, Frijlink HW. Inhalation of tobramycin in Cystic Fibrosis. Part 1: The choice of a nebulizer. Int J Pharm 1999;189:205-14.

    Article  CAS  PubMed  Google Scholar 

  21. Geller DE. Choosing a nebulizer for cystic fibrosis applications. Curr Opin Pulm Med 1997;6:414-9.

    Article  Google Scholar 

  22. Mattews LW, Doershuk CF. Inhalation therapy and postural drainage for the treatment of cystic fibrosis. Mod Probl Pediatr 1967;10:297-314.

    Google Scholar 

  23. Newman SP, Pellow PGD, Clarke SW. Droplet size distribution of nebulised aerosols for inhalation therapy. Clin Phys Physiol Meas 1986;7:139-46.

    Article  CAS  PubMed  Google Scholar 

  24. Mercer TT. Production of therapeutic aerosols: principles and techniques. Chest 1981;80 (suppl):813-8.

    CAS  PubMed  Google Scholar 

  25. Sterk PJ, Plomp A, Van der Vate JF, Quanjer PH. Physical properties of aerosols produced by several jet and ultrasonic nebulizers. Bull Eur Physiolpathol Respir 1984;20:65-72.

    CAS  Google Scholar 

  26. Hinds WC. Aerosol technology. Properties, behavior and measurement of airborne particles. John Wiley & Sons, New York, 1982

    Google Scholar 

  27. Le Brun PPH, de Boer AH, Gjaltema D, Hagedoorn P, Heijerman HGM, Frijlink HW. Inhalation of tobramycin in Cystic Fibrosis. Part 2: Optimization of the tobramycin solution for a jet and an ultrasonic nebulizer. Int J Pharm 1999;189:215-25

    Article  CAS  PubMed  Google Scholar 

  28. Nukiyama S, Tanasawa Y. Experiments on the atomisation of liquid by means of an air stream. Trans Soc Mech 1939;6:18-131.

    Google Scholar 

  29. Clay MM, Pavia D, Newman SP, Lennard-Jones T, Clarke SW. Assesment of jet nebulizers for lung aerosol therapy. Lancet 1983 (II):592-4.

    Article  Google Scholar 

  30. Lang RJ. Ultrasonic atomization of liquids. J Acoustics Soc Am 1962,34:6-8.

    Article  Google Scholar 

  31. Newman SP, Pellow PGD, Clarke SW. Dropsizes from medical atomisers for drug solutions with different viscosities and surface tensions. Atomization and Spray Technolog 1987;3:1-11.

    CAS  Google Scholar 

  32. McCallion ONM, Tayler KMG, Thomas M, Taylor AJ. Nebulisation of fluids of different physicochemical properties with air-jet and ultrasonic nebulizers. Pharm Research 1995;12:1682-8.

    Article  CAS  Google Scholar 

  33. Hinds WC, Macher JM, Firts MW. Size distribution of aerosols produced by the Laskin aerosol generator using substitute materials for DOP. Am Ind Hyg Ass J 1983; 44:495-500.

    Article  CAS  Google Scholar 

  34. Boucher RMG, Kreuter J. The fundamentals of the ultrasonic atomization of medicated solutions. Ann allergy 1968;26: 591-600.

    CAS  PubMed  Google Scholar 

  35. McCallion ONM, Taylor KMG, Thomas M, Taylor AJ. Ultrasonic nebulisation of fluids with different viscosities and surface tensions. J Aerosol Med 1995;8:281-4.

    Article  Google Scholar 

  36. Newman SP, Pitcairn GR, Hooper G, Knoch M. Efficient drug delivery to the lungs from a continuously operated openvent nebulizer and low pressure compressor system. Eur Resp J 1994;7:1177-81.

    CAS  Google Scholar 

  37. Devadson SG, Everard ML, Linto JM, Le Souëf PN. Comparison of drug delivery from conventional versus "Venturi" nebulizers. Eur Resp J 1997;10:2479-83.

    Article  Google Scholar 

  38. Coates AL, MacNeish CF, Lands LC, Meisner D, Keleman S, Vadas EB. A comparison of the availability of tobramycin for inhalation from vented vs unvented nebulizers. Chest 1998;113:951-6.

    Article  CAS  PubMed  Google Scholar 

  39. Newman SP, Pellow PGD, Clarke SW. Evaluation of jet nebulizers for use with gentamicin solutions. Thorax 1985;40:671-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Touw DJ, Jacobs FAH, Brimicombe RW, Heijerman HGM, Bakker W, Breimer DD. Pharmacokinetics of aerosolized tobramycin in adult patients with cystic fibrosis. Antimicrob Agents Chemother 1997;41:184-7.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Le Brun PPH, Vinks AATMM, Touw DJ, Hekelaar N, Mannes GPM, Brimicombe RW, Frijlink HW, Heijerman HGM. Can tobramycin inhalation be improved with a jet nebulizer; A pharmacokinetic analysis. Ther Drug Mon 1999;21:618-24.

    Article  CAS  Google Scholar 

  42. Schöni MH. Compliance der Inhalationstherapie bei Kindern mit respiratorischen erkrankungen. Schweiz Rundsch Med Prax 1993;82:1218-21.

    PubMed  Google Scholar 

  43. Cochrane GM. Compliance with nebulized therapy. Eur Respir Rev 1997;7:51:383-4.

    Google Scholar 

  44. Le Brun PPH, Brimicombe RW, van Doorne H, Heijerman HGM. The cleaning and disinfection of nebulizers used at home and in a cystic fibrosis center. Eur Hosp Pharm 2000; accepted for publication

  45. Laube BL. Measurement of aerosol deposition in CF. Pediatric Pulmonol 1998 (suppl 17):181-2.

    Google Scholar 

  46. Chua HL, Coliis GG, Newburry AM, Chan K, Bower GD, Sly PD, Le Souef PN. The influence of age on aerososl deposition in infants with cystic fibrosis. Eur Respir J 1994;7:2185-91.

    Article  CAS  PubMed  Google Scholar 

  47. Mallol J, Rattray S, Walker G, Cook D, Robertson CF. Aerosol deposition in children with cystic fibrosis. Pediatric Pulmonol 1996;21:276-81.

    Article  CAS  Google Scholar 

  48. Clark A. New aerosol delivery systems for cystic fibrosis. Ped Pulmonol 1998; suppl 17:183-4.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Central Hospital Pharmacy The Hague, P.O. Box 43100, 2504 AC, Den Haag, The Netherlands

    P.P.H. Le Brun

  2. Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Groningen, The Netherlands

    A.H. de Boer & H.W. Frijlink

  3. Adult Cystic Fibrosis Center, Department of Pulmonology, Leyenburg Hospital, Den Haag, The Netherlands

    H.G.M. Heijerman

Authors
  1. P.P.H. Le Brun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A.H. de Boer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H.W. Frijlink
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H.G.M. Heijerman
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Le Brun, P., de Boer, A., Frijlink, H. et al. A review of the technical aspects of drug nebulization. Pharm World Sci 22, 75–81 (2000). https://doi.org/10.1023/A:1008786600530

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1008786600530

Search

Navigation