Understanding the mechanisms underlying pulsating aerosol delivery to the maxillary sinus: In vitro tests and computational simulations

Int J Pharm. 2017 Mar 30;520(1-2):254-266. doi: 10.1016/j.ijpharm.2017.02.017. Epub 2017 Feb 9.

Abstract

Background: Pulsating aerosol delivery has been demonstrated in depositing medications into paranasal sinuses. However, its mechanisms are not fully understood. Influences of the nasal anatomy and sound frequency on intrasinus delivery are not yet clear.

Objectives: This study aimed to gain a better understanding of the mechanisms for enhanced intrasinus delivery with pulsating sound. Specifically, effects of the pulsation frequency, ostium size, and sinus shape on the intrasinus dosage and resonance frequency would be examined.

Methods and materials: Both experiments and computational modeling were conducted to understand the pulsating aerosol delivery in both idealized (two-bottle) and realistic nose-sinus models. A computational model of intrasinus pulsation delivery was developed using COMSOL and was cross-validated with both experimental and theoretical results.

Results: In contrast to previous studies, seemingly erratic relations between the intrasinus dosage and ostium diameter were observed in experiments, which suggested a more complicated particle transport mechanism. Improved agreement was achieved when grouping the ostium size and sinus volume into the resonance frequency, and therefore, validated the hypothesis that intrasinus deposition strongly depends on the resonance frequency. Extensive computational simulations revealed that the deposition was highest at the resonance frequency and decreased gradually at off-resonance frequencies. The resonance frequency depended on the ostium and sinus morphology, but was independent of the nasal cavity.

Conclusion: Results of this study verified the hypothesis of resonance being the mechanism for enhanced particle deposition in the maxillary sinus. A better knowledge of the relationship between sinus dosages, pulsating frequency, and nasal morphometry is essential for improving the design of intrasinus delivery devices.

Keywords: Chronic rhinosinusitis; Maxillary sinus; Pulsating aerosol; Resonance frequency.

MeSH terms

  • Administration, Intranasal
  • Aerosols / administration & dosage
  • Aerosols / pharmacokinetics*
  • Computer Simulation*
  • Humans
  • In Vitro Techniques
  • Maxillary Sinus / anatomy & histology
  • Maxillary Sinus / metabolism*
  • Nasal Cavity / anatomy & histology
  • Nasal Cavity / metabolism
  • Reproducibility of Results
  • Sound

Substances

  • Aerosols