Skip to main content
SpringerLink
Log in

In Vitro Assessment of Spray Deposition Patterns in a Pediatric (12 Year-Old) Nasal Cavity Model

  • Research Paper
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose

Nasal sprays available for the treatment of cold and allergy symptoms currently use identical formulations and devices for adults as well as for children. Due to the obvious differences between the nasal airway dimensions of a child and those of an adult, the performance of nasal sprays in children was evaluated.

Methods

Deposition patterns of nasal sprays administered to children were tested using a nasal cast based on MRI images obtained from a 12 year old child’s nasal cavity. Test formulations emitting a range of spray patterns were investigated by actuating the device into the pediatric nasal cast under controlled conditions.

Results

The results showed that the nasal sprays impacted in the anterior region of the 12 year old child’s nasal cavity, and only limited spray entered the turbinate region – the effect site for most topical drugs and the primary absorptive region for systemically absorbed drugs.

Conclusion

Differences in deposition patterns following the administration of nasal sprays to adults and children may lead to differences in efficacy between these populations. Greater anterior deposition in children may result in decreased effectiveness, greater anterior dosage form loss, and the increased potential for patient non-compliance.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Foo MY, Cheng YS, Su WC, Donovan MD. The influence of spray properties on intranasal deposition. J Aerosol Med. 2007;20(4):495–508.

    Article  CAS  PubMed  Google Scholar 

  2. Kundoor V, Dalby RN. Effect of formulation and administration related variables on deposition pattern of nasal spray pumps evaluated using a nasal cast. Pharm Res. 2011;28(8):1895–904.

    Article  CAS  PubMed  Google Scholar 

  3. Dayal P, Shaik MS, Singh M. Evaluation of different parameters that affect droplet-size distribution from nasal sprays using the Malvern Spraytec. J Pharm Sci. 2004;93(7):1725–42.

    Article  CAS  PubMed  Google Scholar 

  4. Cheng Y, Holmes T, Gao J, Guilmette R, Li S, Surakitbanharn Y, et al. Characterization of nasal spray pumps and deposition pattern in a replica of the human nasal airway. J Aerosol Med. 2001;14(2):267–80.

    Article  CAS  PubMed  Google Scholar 

  5. Arora P, Sharma S, Garg S. Permeability issues in nasal drug delivery. Drug Discov Today. 2002;7(18):967–75.

    Article  CAS  PubMed  Google Scholar 

  6. Kesavanathan J, Bascom R, Swift DL. The effect of nasal passage characteristics on particle deposition. J Aerosol Med. 1998;11(1):27–39.

    Article  Google Scholar 

  7. Howard BK, Rohrich RJ. Understanding the nasal airway: principles and practice. Plast Reconstr Surg. 2002;109(3):1128–46.

    Article  PubMed  Google Scholar 

  8. Djupesland PG. Nasal drug delivery devices: characteristics and performance in a clinical perspective-a review. Drug Deliv Transl Res. 2013;3(1):42–62.

    Article  CAS  PubMed  Google Scholar 

  9. Xi J, Si X, Kim JW, Berlinski A. Simulation of airflow and aerosol deposition in the nasal cavity of a 5-year-old child. J Aerosol Sci. 2011;42(3):156–73.

    Article  CAS  Google Scholar 

  10. Kublik H, Vidgren M. Nasal delivery systems and their effect on deposition and absorption. Adv Drug Deliv Rev. 1998;29(1):157–77.

    Article  CAS  PubMed  Google Scholar 

  11. Swift DL, Proctor DF. Access of air to the respiratory tract. Respir Def Mech. 1977;5(part 1):63–93.

    Google Scholar 

  12. Antunes MB, Cohen NA. Mucociliary clearance–a critical upper airway host defense mechanism and methods of assessment. Curr Opin Allergy Clin Immunol. 2007;7(1):5–10.

    Article  PubMed  Google Scholar 

  13. Andersen I, Proctor D. Measurement of nasal mucociliary clearance. Eur J Respir Dis Suppl. 1982;127:37–40.

    Google Scholar 

  14. Schipper NG, Verhoef JC, Merkus FW. The nasal mucociliary clearance: relevance to nasal drug delivery. Pharm Res. 1991;8(7):807–14.

    Article  CAS  PubMed  Google Scholar 

  15. Marttin E, Schipper NG, Verhoef JC, Merkus FW. Nasal mucociliary clearance as a factor in nasal drug delivery. Adv Drug Deliv Rev. 1998;29(1):13–38.

    Article  CAS  PubMed  Google Scholar 

  16. Pires A, Fortuna A, Alves G, Falcão A. Intranasal drug delivery: how, why and what for? J Pharm Pharm Sci. 2009;12(3):288–311.

    Article  CAS  PubMed  Google Scholar 

  17. USFDA. Guidance for Industry “Bioavailability and bioequivalence studies for nasal aerosols and nasal sprays for local action”. Center for Drug Evaluation and Research (CDER), Rockville, MD. 2003.

  18. Frank DO, Kimbell JS, Pawar S, Rhee JS. Effects of anatomy and particle size on nasal sprays and nebulizers. Otolaryngol Head Neck Surg. 2012;146(2):313–9.

    Article  PubMed  Google Scholar 

  19. Suman JD, Laube BL, Dalby R. Comparison of nasal deposition and clearance of aerosol generated by a nebulizer and an aqueous spray pump. Pharm Res. 1999;16(10):1648–52.

    Article  CAS  PubMed  Google Scholar 

  20. Suman JD. Current understanding of nasal morphology and physiology as a drug delivery target. Drug Deliv Transl Res. 2013;3(1):4–15.

    Article  CAS  PubMed  Google Scholar 

  21. Hallworth G, Padfield J. A comparison of the regional depesition in a model nose of a drug discharged from metered serosel and metered-pump nasal delivery systems. J Allergy Clin Immunol. 1986;77(2):348–53.

    Article  CAS  PubMed  Google Scholar 

  22. Rygg A, Hindle M, Longest PW. Linking suspension nasal spray drug deposition patterns to pharmacokinetic profiles: a proof-of-concept study using computational fluid dynamics. J Pharm Sci. 2016;105(6):1995–2004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ghahramani E, Abouali O, Emdad H, Ahmadi G. Numerical analysis of stochastic dispersion of micro-particles in turbulent flows in a realistic model of human nasal/upper airway. J Aerosol Sci. 2014;67:188–206.

    Article  CAS  Google Scholar 

  24. Golshahi L, Noga M, Thompson R, Finlay W. In vitro deposition measurement of inhaled micrometer-sized particles in extrathoracic airways of children and adolescents during nose breathing. J Aerosol Sci. 2011;42(7):474–88.

    Article  CAS  Google Scholar 

  25. Bennett WD, Zeman KL, Jarabek AM. Nasal contribution to breathing and fine particle deposition in children versus adults. J Toxicol Environ Health A. 2007;71(3):227–37.

    Article  Google Scholar 

  26. Xi J, Berlinski A, Zhou Y, Greenberg B, Ou X. Breathing resistance and ultrafine particle deposition in nasal–laryngeal airways of a newborn, an infant, a child, and an adult. Ann Biomed Eng. 2012;40(12):2579–95.

    Article  PubMed  Google Scholar 

  27. Cheng Y-S, Smith SM, Yeh H-C, Kim D-B, Cheng K-H, Swift DL. Deposition of ultrafine aerosols and Thoron progeny in replicas of nasal Airways of Young Children. Aerosol Sci Technol. 2007;23(4):541–52.

    Article  Google Scholar 

  28. Becquemin MH, Swift DL, Bouchikhi A, Roy M, Teillac A. Particle deposition and resistance in the noses of adults and children. Eur Respir J. 1991;4(6):694–702.

    CAS  PubMed  Google Scholar 

  29. Xi J, Si X, Zhou Y, Kim J, Berlinski A. Growth of nasal-laryngeal airways in children and their implications in breathing and inhaled aerosol dynamics. Respir Care. 2013;59(2):263–73.

    Article  PubMed  Google Scholar 

  30. List SJ, Findlay BP, Forstner G, Forstner J. Enhancement of the viscosity of mucin by serum albumin. Biochem J. 1978;175(2):565–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Laube BL, Sharpless G, Vikani AR, Harrand V, Zinreich SJ, Sedberry K, et al. Intranasal deposition of Accuspray™ aerosol in anatomically correct models of 2-, 5-, and 12-year-old children. J Aerosol Med Pulm Drug Deliv. 2015;28(5):320–33.

    Article  CAS  PubMed  Google Scholar 

  32. Makidon PE, Nigavekar SS, Bielinska AU, Mank N, Shetty AM, Suman J, et al. Characterization of stability and nasal delivery systems for immunization with nanoemulsion-based vaccines. J Aerosol Med Pulm Drug Deliv. 2010;23(2):77–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Warnken ZN, Smyth HDC, Davis DA, Weitman S, Kuhn JG, Williams RO. Personalized medicine in nasal delivery: the use of patient-specific administration parameters to improve nasal drug targeting using 3D-printed nasal replica casts. Mol Pharm. 2018. https://doi.org/10.1021/acs.molpharmaceut.7b00702.

  34. Foo MY. Deposition pattern of nasal sprays in the human nasal airway: interactions among formulation, device, anatomy and administration techniques. Ph.D. Dissertation, University of Iowa, Iowa City, IA: ProQuest; 2007.

  35. Guo Y, Laube B, Dalby R. The effect of formulation variables and breathing patterns on the site of nasal deposition in an anatomically correct model. Pharm Res. 2005;22(11):1871–8.

    Article  CAS  PubMed  Google Scholar 

  36. Xi J, Yuan JE, Zhang Y, Nevorski D, Wang Z, Zhou Y. Visualization and quantification of nasal and olfactory deposition in a sectional adult nasal airway cast. Pharm Res. 2016;33(6):1527–41.

    Article  CAS  PubMed  Google Scholar 

  37. Pu Y, Goodey AP, Fang X, Jacob K. A comparison of the deposition patterns of different nasal spray formulations using a nasal cast. Aerosol Sci Technol. 2014;48(9):930–8.

    Article  CAS  Google Scholar 

  38. Chabacano. Olfactory System [Internet]. Wikimedia Commons. Copyright information: Creative Commons Attribution-ShareAlike (CC BY-SA 2.5) [cited 2017 Oct 14]. Available from: https://upload.wikimedia.org/wikipedia/commons/2/20/Olfactory_system.svg

Download references

ACKNOWLEDGMENTS AND DISCLOSURES

This study was funded by an FDA Grant to the National Institute for Pharmaceutical Technology and Education (NIPTE) titled "The Critical Path Manufacturing Sector Research Initiative (U01)"; Grant# 5U01FD004275.

The results and conclusions presented reflect the opinions of the authors and not those of the funding agencies.

Author information

Authors and Affiliations

  1. Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, 115 S Grand Avenue, Iowa City, Iowa, 52242, USA

    Namita Sawant & Maureen D. Donovan

Authors
  1. Namita Sawant
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maureen D. Donovan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maureen D. Donovan.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sawant, N., Donovan, M.D. In Vitro Assessment of Spray Deposition Patterns in a Pediatric (12 Year-Old) Nasal Cavity Model. Pharm Res 35, 108 (2018). https://doi.org/10.1007/s11095-018-2385-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11095-018-2385-6

Key Words

Search

Navigation