Comparison of Sinus Deposition from an Aqueous Nasal Spray and Pressurised MDI in a Post-Endoscopic Sinus Surgery Nasal Replica.
Administration, Inhalation
Drug Compounding
Female
Fluticasone
/ administration & dosage
Glucocorticoids
/ administration & dosage
Humans
Metered Dose Inhalers
Middle Aged
Models, Anatomic
Nasal Sprays
Paranasal Sinuses
/ anatomy & histology
Printing, Three-Dimensional
Tissue Distribution
Transanal Endoscopic Surgery
Administration, intranasal
Administration, topical
Drug delivery systems
Nasal airflow, Nasal cavity, Nasal spray
Paranasal sinuses
Sinusitis
Journal
Pharmaceutical research
ISSN: 1573-904X
Titre abrégé: Pharm Res
Pays: United States
ID NLM: 8406521
Informations de publication
Date de publication:
Feb 2022
Feb 2022
Historique:
received:
09
07
2021
accepted:
17
10
2021
pubmed:
10
2
2022
medline:
11
3
2022
entrez:
9
2
2022
Statut:
ppublish
Résumé
Optimising intranasal distribution and retention of topical therapy is essential for effectively managing patients with chronic rhinosinusitis, including those that have had functional endoscopic sinus surgery (FESS). This study presents a new technique for quantifying in vitro experiments of fluticasone propionate deposition within the sinuses of a 3D-printed model from a post-FESS patient. Circular filter papers were placed on the sinus surfaces of the model. Deposition of fluticasone on the filter paper was quantified using high-performance liquid chromatography (HPLC) assay-based techniques. The deposition patterns of two nasal drug delivery devices, an aqueous nasal spray (Flixonase) and metered dose inhaler (Flixotide), were compared. The effects of airflow (0 L/min vs. 12 L/min) and administration angle (30° vs. and 45°) were evaluated. Inhaled airflow made little difference to sinus deposition for either device. A 45° administration angle improved frontal sinus deposition with the nasal spray and both ethmoidal and sphenoidal deposition with the inhaler. The inhaler provided significantly better deposition within the ethmoid sinuses (8.5x) and within the maxillary sinuses (3.9x) compared with the nasal spray under the same conditions. In the post-FESS model analysed, the inhaler produced better sinus deposition overall compared with the nasal spray. The techniques described can be used and adapted for in vitro performance testing of different drug formulations and intranasal devices under different experimental conditions. They can also help validate computational fluid dynamics modelling and in vivo studies.
Sections du résumé
BACKGROUND
BACKGROUND
Optimising intranasal distribution and retention of topical therapy is essential for effectively managing patients with chronic rhinosinusitis, including those that have had functional endoscopic sinus surgery (FESS). This study presents a new technique for quantifying in vitro experiments of fluticasone propionate deposition within the sinuses of a 3D-printed model from a post-FESS patient.
METHODS
METHODS
Circular filter papers were placed on the sinus surfaces of the model. Deposition of fluticasone on the filter paper was quantified using high-performance liquid chromatography (HPLC) assay-based techniques. The deposition patterns of two nasal drug delivery devices, an aqueous nasal spray (Flixonase) and metered dose inhaler (Flixotide), were compared. The effects of airflow (0 L/min vs. 12 L/min) and administration angle (30° vs. and 45°) were evaluated.
RESULTS
RESULTS
Inhaled airflow made little difference to sinus deposition for either device. A 45° administration angle improved frontal sinus deposition with the nasal spray and both ethmoidal and sphenoidal deposition with the inhaler. The inhaler provided significantly better deposition within the ethmoid sinuses (8.5x) and within the maxillary sinuses (3.9x) compared with the nasal spray under the same conditions.
CONCLUSION
CONCLUSIONS
In the post-FESS model analysed, the inhaler produced better sinus deposition overall compared with the nasal spray. The techniques described can be used and adapted for in vitro performance testing of different drug formulations and intranasal devices under different experimental conditions. They can also help validate computational fluid dynamics modelling and in vivo studies.
Identifiants
pubmed: 35137359
doi: 10.1007/s11095-021-03129-2
pii: 10.1007/s11095-021-03129-2
pmc: PMC8881262
doi:
Substances chimiques
Glucocorticoids
0
Nasal Sprays
0
Fluticasone
CUT2W21N7U
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
317-327Informations de copyright
© 2022. The Author(s).
Références
DeConde AS, Soler ZM. Chronic rhinosinusitis: Epidemiology and burden of disease. Am J Rhinol Allergy. 2016;30(2):134–9.
doi: 10.2500/ajra.2016.30.4297
Fokkens W, Lund V, Hopkins C, Hellings PW, Kern R, Reitsma S, et al. European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Rhinology journal. 2020;58:1–464.
doi: 10.4193/Rhin20.401
Orlandi RR, Kingdom TT, Hwang PH, Smith TL, Alt JA, Baroody FM, et al. International Consensus Statement on Allergy and Rhinology: Rhinosinusitis. Int Forum Allergy Rhinol. 2016;6(Suppl 1):S22-209.
Fung MC, Inthavong K, Yang W, Tu J. CFD Modeling of Spray Atomization for a Nasal Spray Device. Aerosol Sci Technol. 2012;46(11):1219–26.
doi: 10.1080/02786826.2012.704098
Kimbell JS, Segal RA, Asgharian B, Wong BA, Schroeter JD, Southall JP, et al. Characterisation of deposition from nasal spray devices using a computational fluid dynamics model of the human nasal passages. J Aerosol Med. 2007;20(1):59–74.
doi: 10.1089/jam.2006.0531
Calmet H, Kleinstreuer C, Houzeaux G, Kolanjiyil A, Lehmkuhl O, Olivares E, et al. Subject-variability effects on micron particle deposition in human nasal cavities. J Aerosol Sci. 2018;115:12–28.
doi: 10.1016/j.jaerosci.2017.10.008
Kelly JT, Asgharian B, Kimbell JS, BA W. Particle deposition in human nasal airway replicas manufactured by different methods Part 1: Inertial regime particles. Aerosol Science and Technology. 2004;38(11):1063–71.
doi: 10.1080/027868290883360
Kiaee M, Wachtel H, Noga ML, Martin AR, Finlay WH. An idealised geometry that mimics average nasal spray deposition in adults: A computational study. Comput Biol Med. 2019;107:206–17.
doi: 10.1016/j.compbiomed.2019.02.013
Liu Y, Matida EA, Johnson MR. Experimental measurements and computational modeling of aerosol deposition in the Carleton-Civic standardised human nasal cavity. J Aerosol Sci. 2010;41(6):569–86.
doi: 10.1016/j.jaerosci.2010.02.014
Ge QJ, Inthavong K, Tu JY. Local deposition fractions of ultrafine particles in a human nasal-sinus cavity CFD model. Inhal Toxicol. 2012;24(8):492–505.
doi: 10.3109/08958378.2012.694494
Hood CM, Schroter RC, Doorly DJ, Blenke EJSM, Tolley NS. Computational modeling of flow and gas exchange in models of the human maxillary sinus. J Appl Physiol. 2009;107(4):1195–203.
doi: 10.1152/japplphysiol.91615.2008
Xiong G, Zhan J, Zuo K, Li J, Rong L, Xu G. Numerical flow simulation in the post-endoscopic sinus surgery nasal cavity. Med Biol Eng Compu. 2008;46(11):1161–7.
doi: 10.1007/s11517-008-0384-1
Bleier BS, Debnath I, Harvey RJ, Schlosser RJ. Temporospatial quantification of fluorescein-labeled sinonasal irrigation delivery. Int Forum Allergy Rhinol. 2011;1:361–5.
doi: 10.1002/alr.20041
Djupesland PG, Skretting A. Nasal deposition and clearance in man: comparison of a bidirectional powder device and a traditional liquid spray pump. J Aerosol Med Pulm Drug Deliv. 2012;25:280–9.
doi: 10.1089/jamp.2011.0924
Merkus P, Ebbens FA, Muller B, Fokkens WJ. The “best method” of topical nasal drug delivery: comparison of seven techniques. Rhinology. 2006;44:102–7.
Tay SY, Chao SS, Mark KT, Wang Y. Comparison of the distribution of intranasal steroid spray using different application techniques. Int Forum Allergy Rhinol. 2016;6:1204–10.
doi: 10.1002/alr.21807
Thomas WW, Harvey RJ, Rudmik L, Hwang PH, Schlosser RJ. Distribution of topical agents to the paranasal sinuses: an evidence-based review with recommendations. Int Forum Allergy Rhinol. 2013;3:691–703.
doi: 10.1002/alr.21172
Weber R, Keerl R, Radziwill R, Schick B, Jaspersen D, Dshambazov K, et al. Videoendoscopic analysis of nasal steroid distribution. Rhinology. 1999;37(2):69–73.
pubmed: 10416252
Scheibe M, Bethge C, Witt M, Hummel T. Intranasal administration of drugs. Arch Otolaryngol Head Neck Surg. 2008;134:643–6.
doi: 10.1001/archotol.134.6.643
Rudman KL, O’Brien EK, Leopold DA. Radiographic distribution of drops and sprays within the sinonasal cavities. Am J Rhinol Allergy. 2011;25:94–7.
Siu J, Johnston JJ, Pontre B, Inthavong K, Douglas RG. Magnetic resonance imaging evaluation of the distribution of spray and irrigation devices within the sinonasal cavities. Int Forum Allergy Rhinol. 2019;9(9):958–70.
doi: 10.1002/alr.22376
Suman JD, Laube BL, Dalby R. Comparison of nasal deposition and clearance of aerosol generated by nebuliser and an aqueous spray pump. Pharm Res. 1999;16(10):1648–52.
doi: 10.1023/A:1011933410898
Siu J, Dong J, Inthavong K, Shang Y, Douglas RG. Quantification of airflow in the sinuses following functional endoscopic sinus surgery. Rhinology. 2020;58(3):257–65.
pubmed: 32238994
Frank DO, Zanation AM, Dhandha VH, McKinney KA, Fleischman GM, Ebert CS Jr, et al. Quantification of airflow into the maxillary sinuses before and after functional endoscopic sinus surgery. Int Forum Allergy Rhinol. 2013;3(10):834–40.
doi: 10.1002/alr.21203
Wofford MR, Kimbell JS, Frank-Ito DO, Dhandha V, McKinney KA, Fleischman GM, et al. A computational study of functional endoscopic sinus surgery and maxillary sinus drug delivery. Rhinology. 2015;53(1):41–8.
doi: 10.4193/Rhino13.065
Siu J, Shrestha K, Inthavong K, Shang Y, Douglas R. Particle deposition in the paranasal sinuses following endoscopic sinus surgery. Comput Biol Med. 2020;116:103573.
AR SC, Cardoso DE, Cabral-Marques HM. Validation of an HPLC Analytical Method for the Quantitative/Qualitative Determination of Fluticasone Propionate in Inhalation Particles on Several Matrices. Scientia pharmaceutica. 2014;82(4):787–97.
Rennie CE, Gouder KA, Taylor DJ, Tolley NS, Schroter RC, Doorly DJ. Nasal inspiratory flow: at rest and sniffing. Int Forum Allergy Rhinol. 2011;1(2):128–35.
doi: 10.1002/alr.20021
Fung MC, Inthavong K, Yang W, Lappas P, Tu J. External characteristics of unsteady spray atomisation from a nasal spray device. J Pharm Sci. 2013;102(3):1024–35.
doi: 10.1002/jps.23449
Newman SP, Pitcairn GR, Dalby RN. Drug delivery to the nasal cavity: in vitro and in vivo assessment. Crit Rev Ther Drug Carrier Syst. 2004;21(1):21–66.
doi: 10.1615/CritRevTherDrugCarrierSyst.v21.i1.20
Suman JD, Laube BL, Lin TC, Brouet G, Dalby R. Validity of in vitro tests on aqueous spray pumps as surrogates for nasal deposition. Pharma Res. 2002;19(1):1–6.
doi: 10.1023/A:1013643912335
Inthavong K, Fung MC, Tong X, Yang W, Tu J. High Resolution Visualization and Analysis of Nasal Spray Drug Delivery. Pharmaceutical Research. 2014:1–8.
Inthavong K, Fung MC, Yang W, Tu J. Measurements of droplet size distribution and analysis of nasal spray atomisation from different actuation pressure. J Aerosol Med Pulm Drug Deliv. 2015;28(1):59–67.
doi: 10.1089/jamp.2013.1093
Calmet H, Houzeaux G, Vázquez M, Eguzkitza B, Gambaruto AM, Bates AJ, et al. Flow features and micro-particle deposition in a human respiratory system during sniffing. J Aerosol Sci. 2018;123:171–84.
doi: 10.1016/j.jaerosci.2018.05.008
Cheng YS, Holmes TD, Gao J, Guilmette RA, Li S, Surakitbanharn Y, et al. Characterisation of Nasal Spray Pumps and Deposition Pattern in a Replica of the Human Nasal Airway. J Aerosol Med. 2001;14(2):267–80.
doi: 10.1089/08942680152484199
Schroeter JD, Garcia GJM, Kimbell JS. Effects of surface smoothness on inertial particle deposition in human nasal models. J Aerosol Sci. 2011;42(1):52–63.
doi: 10.1016/j.jaerosci.2010.11.002
Shang Y, Inthavong K. Numerical assessment of ambient inhaled micron particle deposition in a human nasal cavity. Experimental and Computational Multiphase Flow. 2019;1(2):109–15.
doi: 10.1007/s42757-019-0015-0
Chen Y, Young PM, Murphy S, Fletcher DF, Long E, Lewis D, et al. High-Speed Laser Image Analysis of Plume Angles for Pressurised Metered Dose Inhalers: The Effect of Nozzle Geometry. AAPS PharmSciTech. 2017;18(3):782–9.
doi: 10.1208/s12249-016-0564-5
Oliveira R, Teixeira S, F L, Antunes H. pMDI Sprays : Theory , Experiment and Numerical Simulation. 2012. p. 300.
Foo MY, Cheng YS, Su WC, Donovan MD. The influence of spray properties on intranasal deposition. J Aerosol Med 2007;20(495–508).
Liu X, Doub WH, Guo C. Evaluation of metered dose inhaler spray velocities using phase Doppler anemometry (PDA). Int J Pharm. 2012;423(2):235–9.
doi: 10.1016/j.ijpharm.2011.12.006
Mygind N, Vesterhauge S. Aerosol distribution in the nose. Rhinology. 1978;16(2):79–88.
pubmed: 684327
Newman SP, Morén F, Clarke SW. Deposition pattern from a nasal pump spray. Rhinology. 1987;25(2):77–82.
pubmed: 3616395
Subramaniam RP, Richardson RB, Morgan KT, Kimbell JS, Guilmette RA. Computational fluid dynamics simulations of inspiratory airflow in the human nose and nasopharynx. Inhalation Toxicol. 1998;10(2):91–120.
doi: 10.1080/089583798197772
Djupesland P, Messina J, Palmer J. Deposition of drugs in the nose and sinuses with an exhalation delivery system vs conventional nasal spray or high-volume irrigation in Draf II/III post-surgical anatomy. Rhinology journal. 2019;58.
U.S. Food and Drug Administration: Guidance for Industry: Nasal Spray and Inhalation Solution, Suspension, and Spray Drug Products—Chemistry, Manufacturing, and Controls Documentation. U.S. Food and Drug Administration, Washington, DC; 2002.
Kundoor V, Dalby RN. Assessment of nasal spray deposition pattern in a silicone human nose model using a color-based method. Pharm Res. 2010;27(1):30–6.
doi: 10.1007/s11095-009-0002-4