Visualization and Estimation of Nasal Spray Delivery to Olfactory Mucosa in an Image-Based Transparent Nasal Model
Abstract
:1. Introduction
- (1)
- Visualize the deposition distribution of intranasally administered sprays and subsequent liquid film translocation in the nasal cavity using different angles of administration, head positions, number of spray applications, and inhalation flow rates.
- (2)
- Visualize the effect of formulation viscosity on the dosimetry of intranasal sprays.
- (3)
- Quantify the deposition of intranasal sprays in the olfactory cleft, the turbinate region, the front nose, as well as the nasopharynx.
- (4)
- Examine the results and compare the performance between the different test cases to determine the optimal combination of factors that lead to maximum bioavailability in the olfactory region (i.e., delivery of clinically significant doses).
2. Materials and Methods
2.1. Nasal Cast Model
2.2. Study Design
2.3. Inhaler and Spray Solutions
2.4. Protocol for Nasal Spray Delivery
2.5. Image-Based Estimation of Olfactory Dosimetry
2.6. Statistical Analysis
3. Results
3.1. Characterization of Spray Viscosity and Aerosol Generation
3.2. Vertex-To-Floor Head Position for Olfactory Delivery
3.3. Head Position: 60° Backward Tilt from the Supine Position
3.3.1. Deposition Distribution
3.3.2. Dynamic Formation and Translocation of Liquid Film
3.4. Head Positions of 45° and 30° Backward Tilt from the Supine Position
3.5. Effect of Inhalation Flow Rate
3.6. Effects of Solution Viscosity
3.7. Left-Right Discrepancy in Dosimetry
3.8. Image-Based Olfactory Dosimetry Estimation
3.9. Deposition Sensitivity Analysis to Delivery Variables
4. Discussion
5. Conclusions
- (1)
- The OL dosimetry depended not only on the initial deposition of spray droplets but also on the liquid film translocation.
- (2)
- A two-dose application from the soft-mist inhaler was needed to mobilize the liquid film and enable it to move to the olfactory region.
- (3)
- Recommended OL delivery parameters included: a head position tilting 45–60° backward from the supine position, a nozzle angle ranging 5–10° counterclockwise from the nostril normal, two doses, and no inhalation flow.
- (4)
- With the recommended protocol, a delivery efficiency of 22.7 ± 3.7% was achieved in the strictly defined OL region.
- (5)
- The presence of inhalation flow reduced the liquid film translocation to the OL region, with negligible OL doses at 20 L/min.
- (6)
- The vertex-to-floor head position was not optimal for OL delivery, with lower OL delivery efficiency and higher variability.
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Seifelnasr, A.; Si, X.A.; Xi, J. Visualization and Estimation of Nasal Spray Delivery to Olfactory Mucosa in an Image-Based Transparent Nasal Model. Pharmaceutics 2023, 15, 1657. https://doi.org/10.3390/pharmaceutics15061657
Seifelnasr A, Si XA, Xi J. Visualization and Estimation of Nasal Spray Delivery to Olfactory Mucosa in an Image-Based Transparent Nasal Model. Pharmaceutics. 2023; 15(6):1657. https://doi.org/10.3390/pharmaceutics15061657
Chicago/Turabian StyleSeifelnasr, Amr, Xiuhua April Si, and Jinxiang Xi. 2023. "Visualization and Estimation of Nasal Spray Delivery to Olfactory Mucosa in an Image-Based Transparent Nasal Model" Pharmaceutics 15, no. 6: 1657. https://doi.org/10.3390/pharmaceutics15061657