Skip to main content
SpringerLink
Log in

The Challenges of Paediatric Pulmonary Drug Delivery

  • Chapter
  • First Online:
Pediatric Formulations

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 11))

  • 3809 Accesses

Abstract

The lungs offer a (relatively) easy access route by inhalation for drug delivery, both in terms of topical therapy of lung conditions as well as for systemically acting therapies. In paediatric therapy, it is the former which has been most exploited for the delivery of agents such as bronchodilators, corticosteroids and antibiotics where localized drug delivery can minimize systemic exposure and resultant side-effects.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Kamin W, Kreplin A (2007) Teaching the inhalation manoeuvre to asthmatic children by means of visual feedback. Pneumologie 61(3):150–156 (Article in German)

    Article  CAS  PubMed  Google Scholar 

  2. Lavorini F, Magnan A, Dubus JC, Voshaar T, Corbetta L, Broeders M, Dekhuijzen R, Sanchis J, Viejo JL, Barnes P, Corrigan C, Levy M, Crompton GK (2008) Effect of incorrect use of dry powder inhalers on management of patients with asthma and COPD. Respir Med 102(4):593–604

    Article  PubMed  Google Scholar 

  3. Couriel JM, Child F (2004) Applied physiology: lung function testing in children. Curr Paediatr 14(5):444–451

    Article  Google Scholar 

  4. Amirav I, Newhouse MT (2012) Deposition of small particles in the developing lung. Paediatr Respir Rev 13(2):73–78

    Article  PubMed  Google Scholar 

  5. Iles R, Lister P, Edmunds AT (1999) Crying significantly reduces absorption of aerosolised drug in infants. Arch Dis Child 81(2):163–165

    Article  CAS  PubMed  Google Scholar 

  6. Mastrandrea LD, Quattrin T (2006) Clinical evaluation of inhaled insulin. Adv Drug Deliv Rev 58(9−10):1061–1075

    Article  CAS  PubMed  Google Scholar 

  7. Farr SJ, Otulana BA (2006) Pulmonary delivery of opioids as pain therapeutics. Adv Drug Deliv Rev 58(9−10):1076–1088

    Article  CAS  PubMed  Google Scholar 

  8. Dudgeon DJ, Lertzman M (1998) Dyspnea in the advanced cancer patient. J Pain Symptom Manage 16(4):212–219

    Article  CAS  PubMed  Google Scholar 

  9. Walvoord EC, de la Pena A, Park S, Silverman B, Cuttler L, Rose SR, Cutler G, Drop S, Chipman J (2009) Inhaled growth hormone (GH) compared with subcutaneous GH in children with GH deficiency: pharmacokinetics, pharmacodynamics, and safety. J Clin Endocrinol Metab 94(6):2052–2059

    Article  CAS  PubMed  Google Scholar 

  10. Dunnill MS (1962) Postnatal growth of the lung. Thorax 17:329–333

    Article  Google Scholar 

  11. Musante CJ, Martonen TB (2000) Computer simulations of particle deposition in the developing human lung. J Air Waste Manage Assoc 50(8):1426–1432

    Article  CAS  Google Scholar 

  12. Weibel ER (1963) Morphometry of the human lung. Springer, Berlin

    Google Scholar 

  13. Martonen TB (1993) Mathematical-model for the selective deposition of inhaled pharmaceuticals. J Pharm Sci 82(12):1191–1199

    Article  CAS  PubMed  Google Scholar 

  14. Isaacs KK, Martonen TB (2005) Particle deposition in children’s lungs: theory and experiment. J Aerosol Med (Deposition Clearance and Effects in the Lung) 18(3):337–353

    Article  Google Scholar 

  15. Chua HL, Collis GG, Newbury AM, Chan K, Bower GD, Sly PD, Lesouef PN (1994) The influence of age on aerosol deposition in children with cystic-fibrosis. Eur Respir J 7(12):2185–2191

    Article  CAS  PubMed  Google Scholar 

  16. Wildhaber JH, Dore ND, Wilson JM, Devadason SG, LeSouef PN (1999) Inhalation therapy in asthma: nebulizer or pressurized metered-dose inhaler with holding chamber? In vivo comparison of lung deposition in children. J Pediatr 135(1):28–33

    Article  CAS  PubMed  Google Scholar 

  17. Heyder J (2004) Deposition of inhaled particles in the human respiratory tract and consequences for regional targeting in respiratory drug delivery. Proc Am Thorac Soc 1(4):315–320

    Article  CAS  PubMed  Google Scholar 

  18. Carvalho TC, Peters JI, Williams RO (2011) Influence of particle size on regional lung deposition: what evidence is there? Int J Pharm 406(1−2):1–10

    Article  CAS  PubMed  Google Scholar 

  19. Rostami AA (2009) Computational modeling of Aerosol deposition in respiratory tract: a review. Inhal Toxicol 21(4):262–290

    Article  CAS  PubMed  Google Scholar 

  20. Sbirlea-Apiou G, Lemaire M, Katz I, Conway J, Fleming J, Martonen T (2004) Simulation of the regional manifestation of asthma. J Pharm Sci 93(5):1205–1216

    Article  CAS  PubMed  Google Scholar 

  21. Broeders MEAC, Molema J, Hop WCJ, Folgering HTM (2003) Inhalation profiles in asthmatics and COPD patients: reproducibility and effect of instruction. J Aerosol Med 16(2):131–141

    Article  CAS  PubMed  Google Scholar 

  22. Martonen TB, Katz IM (1993) Deposition patterns of aerosolized drugs within human lungs: effects of ventilatory parameters. Pharm Res 10(6):871–878

    Article  CAS  PubMed  Google Scholar 

  23. Brand P, Friemel I, Meyer T, Schulz H, Heyder J, Haubetainger K (2000) Total deposition of therapeutic particles during spontaneous and controlled inhalations. J Pharm Sci 89(6):724–731

    Article  CAS  PubMed  Google Scholar 

  24. Dubus JC, Anhoj J (2004) Inhaled steroid delivery from small-volume holding chambers depends on age, holding chamber, and interface in children. J Aerosol Med (Deposition Clearance and Effects in the Lung) 17(3):225–230

    Article  CAS  Google Scholar 

  25. Le Souef PN, Devadason SG (2002) Lung dose of inhaled drugs in children with acute asthma. J Aerosol Med (Deposition Clearance and Effects in the Lung) 15(3):347–349

    Article  Google Scholar 

  26. Mallol J, Rattray S, Walker G, Cook D, Robertson CF (1996) Aerosol deposition in infants with cystic fibrosis. Pediatr Pulmonol 21(5):276–281

    Article  CAS  PubMed  Google Scholar 

  27. Schuepp KG, Devadason S, Roller C, Wildhaber FH (2004) A complementary combination of delivery device and drug formulation for inhalation therapy in preschool children. Swiss Med Wkly 134(13−14):198–200

    PubMed  Google Scholar 

  28. Devadason SG, Huang T, Walker S, Troedson R, Le Souef PN (2003) Distribution of technetium-99m-labelled QVAR™ delivered using an Autohaler™ device in children. Eur Respir J 21(6):1007–1011

    Article  CAS  PubMed  Google Scholar 

  29. Anhoj J, Bisgaard H, Lipworth BJ (1999) Effect of electrostatic charge in plastic spacers on the lung delivery of HFA-salbutamol in children. Br J Clin Pharmacol 47(3):333–336

    Article  CAS  PubMed  Google Scholar 

  30. Brambilla G, Ganderton D, Garzia R, Lewis D, Meakin B, Ventura P (1999) Modulation of aerosol clouds produced by pressurised inhalation aerosols. Int J Pharm 186(1):53–61

    Article  CAS  PubMed  Google Scholar 

  31. Murnane D, Martin GP, Marriott C (2008) Investigations into the formulation of metered dose inhalers of salmeterol xinafoate and fluticasone propionate microcrystals. Pharm Res 25(10):2283–2291

    Article  CAS  PubMed  Google Scholar 

  32. Pauwels R, Newman S, Borgstrom L (1997) Airway deposition and airway effects of antiasthma drugs delivered from metered-dose inhalers. Eur Respir J 10(9):2127–2138

    Article  CAS  PubMed  Google Scholar 

  33. Newman SP, Brown J, Steed KP, Reader SJ, Kladders H (1998) Lung deposition of fenoterol and flunisolide delivered using a novel device for inhaled medicines – comparison of RESPIMAT with conventional metered-dose inhalers with and without spacer devices. Chest 113(4):957–963

    Article  CAS  PubMed  Google Scholar 

  34. Hirst PH, Bacon RE, Pitcairn GR, Silvasti M, Newman SP (2001) A comparison of the lung deposition of budesonide from Easyhaler®, Turbuhaler® and pMDI plus spacer in asthmatic patients. Respir Med 95(9):720–727

    Article  CAS  PubMed  Google Scholar 

  35. Dubus JC, Dolovich M (2000) Emitted doses of salbutamol pressurized metered-dose inhaler from five different plastic spacer devices. Fundam Clin Pharmacol 14(3):219–224

    Article  CAS  PubMed  Google Scholar 

  36. Barry PW, O’Callaghan C (1999) A comparative analysis of the particle size output of beclomethasone di propionate, salmeterol xinafoate and fluticasone propionate metered dose inhalers used with the Babyhaler, Volumatic and Aerochamber spacer devices. Br J Clin Pharmacol 47(4):357–360

    Article  CAS  PubMed  Google Scholar 

  37. Clark DJ, Lipworth BJ (1996) Effect of multiple actuations, delayed inhalation and antistatic treatment on the lung bioavailability of salbutamol via a spacer device. Thorax 51(10):981–984

    Article  CAS  PubMed  Google Scholar 

  38. Louca E, Leung K, Coates AL, Mitchell JP, Nagel MW (2006) Comparison of three valved holding chambers for the delivery of fluticasone propionate-HFA to an infant face model. J Aerosol Med (Deposition Clearance and Effects in the Lung) 19(2):160–167

    Article  CAS  Google Scholar 

  39. Geller DE, Weers J, Heuerding S (2011) Development of an inhaled dry-powder formulation of tobramycin using PulmoSphere™ technology. J Aerosol Med Pulm Drug Deliv 24(4):175–182

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Adi H, Larson I, Chiou H, Young P, Traini D, Stewart P (2006) Agglomerate strength and dispersion of salmeterol xinafoate from powder mixtures for inhalation. Pharm Res 23(11):2556–2565

    Article  CAS  PubMed  Google Scholar 

  41. Begat P, Price R, Harris H, Morton DAV, Staniforth JN (2005) The influence of force control agents on the cohesive-adhesive balance in dry powder inhaler formulations. “KONA” Powder Sci and Technol Jpn 23:109

    CAS  Google Scholar 

  42. Kou X, Chan LW, Steckel H, Heng PWS (2012) Physico-chemical aspects of lactose for inhalation. Adv Drug Deliv Rev 64(3):220–232

    Article  CAS  PubMed  Google Scholar 

  43. Buckton G (1997) Characterisation of small changes in the physical properties of powders of significance for dry powder inhaler formulations. Adv Drug Deliv Rev 26(1):17–27

    Article  CAS  PubMed  Google Scholar 

  44. Srichana T, Martin GP, Marriott C (1998) Dry powder inhalers: the influence of device resistance and powder formulation on drug and lactose deposition in vitro. Eur J Pharm Sci 7(1):73–80

    Article  CAS  PubMed  Google Scholar 

  45. Cegla UHU (2004) Pressure and inspiratory flow characteristics of dry powder inhalers. Respir Med 98(Suppl 1):S22–S28

    Article  PubMed  Google Scholar 

  46. Kamps AWA, van Ewijk B, Roorda RJ, Brand PLP (2000) Poor inhalation technique, even after inhalation instructions, in children with asthma. Pediatr Pulmonol 29(1):39–42

    Article  CAS  PubMed  Google Scholar 

  47. Desager KN, Geldhof J, Claes R, De Backer W (2006) Measurement of inspiratory flow through three different dry powder inhalation devices using In-Check™ in children with asthma. Pediatr Asthma Allergy Immunol 19(1):6–13

    Article  Google Scholar 

  48. Bronsky EA, Grossman J, Henis MJ, Gallo PP, Yegen U, Della Cioppa G, Kottakis J, Mehra S (2004) Inspiratory flow rates and volumes with the Aerolizer dry powder inhaler in asthmatic children and adults. Curr Med Res Opin 20(2):131–137

    Article  PubMed  Google Scholar 

  49. Parry-Billings M, Birrell C, Oldham L, O’Callaghan C (2003) Inspiratory flow rate through a dry powder inhaler (Clickhaler®) in children with asthma. Pediatr Pulmonol 35(3):220–226

    Article  PubMed  Google Scholar 

  50. Nielsen KG, Skov M, Klug B, Ifversen M, Bisgaard H (1997) Flow-dependent effect of formoterol dry-powder inhaled from the Aerolizer®. Eur Respir J 10(9):2105–2109

    Article  CAS  PubMed  Google Scholar 

  51. Bisgaard H, Klug B, Sumby BS, Burnell PKP (1998) Fine particle mass from the Diskus inhaler and Turbuhaler inhaler in children with asthma. Eur Respir J 11(5):1111–1115

    Article  CAS  PubMed  Google Scholar 

  52. Wildhaber JH, Devadason SG, Wilson JM, Roller C, Lagana T, Borgstrom L, LeSouef PN (1998) Lung deposition of budesonide from Turbuhaler in asthmatic children. Eur J Pediatr 157(12):1017–1022

    Article  CAS  PubMed  Google Scholar 

  53. Hess DR (2008) Aerosol delivery devices in the treatment of asthma. Respir Care 53(6):699–723

    PubMed  Google Scholar 

  54. Nikander K, Turpeinen M, Wollmer P (1999) The conventional ultrasonic nebulizer proved inefficient in nebulizing a suspension. J Aerosol Med (Deposition Clearance and Effects in the Lung) 12(2):47–53

    Article  CAS  Google Scholar 

  55. Le Brun PPH, de Boer AH, Heijerman HGM, Frijlink HW (2000) A review of the technical aspects of drug nebulization. Pharm World Sci 22(3):75–81

    Article  PubMed  Google Scholar 

  56. Gonda I (1996) Inhalation therapy with recombinant human deoxyribonuclease I. Adv Drug Deliv Rev 19(1):37–46

    Article  CAS  Google Scholar 

  57. Le Brun PPH, de Boer AH, Gjaltema D, Hagedoorn P, Heijerman HGM, Frijlink HW (1999) Inhalation of tobramycin in cystic fibrosis – Part 1: the choice of a nebulizer. Int J Pharm 189(2):205–214

    Article  PubMed  Google Scholar 

  58. Bennett WD, Brown JS, Zeman KL, Hu SC, Scheuch G, Sommerer K (2002) Targeting delivery of aerosols to different lung regions. J Aerosol Med 15(2):179–188

    Article  CAS  PubMed  Google Scholar 

  59. Dhand R, Sohal H (2008) Pulmonary drug delivery system for inhalation therapy in mechanically ventilated patients. Expert Rev Med Devices 5(1):9–18

    Article  CAS  PubMed  Google Scholar 

  60. Newman S, Gee-Turner A (2005) The Omron MicroAir vibrating mesh technology nebuliser, a 21st century approach to inhalation therapy. J Ther Res 5(4):29–33

    Google Scholar 

  61. Collis GG, Cole CH, Lesouef PN (1990) Dilution of nebulized aerosols by air entrainment in children. Lancet 336(8711):341–343

    Article  CAS  PubMed  Google Scholar 

  62. Brodie T, Adalat S (2006) Unilateral fixed dilated pupil in a well child. Arch Dis Child 91(12):961

    Article  CAS  PubMed  Google Scholar 

  63. Everard ML, Clark AR, Milner AD (1992) Drug delivery from jet nebulizers. Arch Dis Child 67(5):586–591

    Article  CAS  PubMed  Google Scholar 

  64. Coates AL, Denk O, Leung K, Ribeiro N, Chan J, Green M, Martin S, Charron M, Edwardes M, Keller M (2011) Higher tobramycin concentration and vibrating mesh technology can shorten antibiotic treatment time in cystic fibrosis. Pediatr Pulmonol 46(4):401–408

    Article  PubMed  Google Scholar 

  65. Nikander K, Arheden L, Denyer J, Cobos N (2003) Parents’ adherence with nebulizer treatment of their children when using an adaptive aerosol delivery (AAD™) system. J Aerosol Med (Deposition Clearance and Effects in the Lung) 16(3):273–281

    Article  Google Scholar 

  66. Keller M, Jauernig J, Schueepp K, Stangl R, Ohl S, Roller C, Devadason S, Wildhaber J (2004) Using infant deposition models to improve inhaler system design. Respiratory Drug Delivery IX, Palm Desert

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacy, University of Hertfordshire, Hatfield, UK

    Darragh Murnane & Marc B. Brown

  2. MedPharm Ltd, Unit 3/Chancellor Court, 50 Occam Road, Surrey Research Park, Guildford, GU2 7AB, UK

    Marc B. Brown

Authors
  1. Darragh Murnane
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marc B. Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Darragh Murnane .

Editor information

Editors and Affiliations

  1. Department of Pharmaceutics Department of Analytical Chemistry, University of Copenhagen, Denmark

    Daniel Bar-Shalom

  2. Pediatric Drug Development & More, klausrose Consulting, Riehen, Switzerland

    Klaus Rose

Rights and permissions

Reprints and permissions

Copyright information

© 2014 American Association of Pharmaceutical Scientists

About this chapter

Cite this chapter

Murnane, D., Brown, M.B. (2014). The Challenges of Paediatric Pulmonary Drug Delivery. In: Bar-Shalom, D., Rose, K. (eds) Pediatric Formulations. AAPS Advances in the Pharmaceutical Sciences Series, vol 11. Springer, New York, NY. https://doi.org/10.1007/978-1-4899-8011-3_18

Download citation

Publish with us

Policies and ethics

Search

Navigation