Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Recent In Vitro and In Silico Advances in the Understanding of Intranasal Drug Delivery

Author(s): John Chen*, Andrew R. Martin and Warren H. Finlay*

Volume 27, Issue 12, 2021

Published on: 12 November, 2020

Page: [1482 - 1497] Pages: 16

DOI: 10.2174/1381612826666201112143230

Price: $65

Abstract

Background: Many drugs are delivered intranasally for local or systemic effect, typically in the form of droplets or aerosols. Due to the high cost of in vivo studies, drug developers and researchers often turn to in vitro or in silico testing when first evaluating the behavior and properties of intranasal drug delivery devices and formulations. Recent advances in manufacturing and computer technologies have allowed for increasingly realistic and sophisticated in vitro and in silico reconstructions of the human nasal airways.

Objective: The study aims to perform a summary of advances in the understanding of intranasal drug delivery based on recent in vitro and in silico studies.

Conclusion: The turbinates are a common target for local drug delivery applications, and while nasal sprays are able to reach this region, there is currently no broad consensus across the in vitro and in silico literature concerning optimal parameters for device design, formulation properties and patient technique which would maximize turbinate deposition. Nebulizers can more easily target the turbinates, but come with the disadvantage of significant lung deposition. Targeting of the olfactory region of the nasal cavity has been explored for the potential treatment of central nervous system conditions. Conventional intranasal devices, such as nasal sprays and nebulizers, deliver very little dose to the olfactory region. Recent progress in our understanding of intranasal delivery will be useful in the development of the next generation of intranasal drug delivery devices.

Keywords: Particle deposition, regional deposition, olfactory region, nasal sprays, nebulizers, nasal valve, nasal replica, CFD.

« Previous Next »
[1]
Tiwari G, Tiwari R, Sriwastawa B, et al. Drug delivery systems: An updated review. Int J Pharm Investig 2012; 2(1): 2-11.
[http://dx.doi.org/10.4103/2230-973X.96920] [PMID: 23071954]
[2]
Tepper DE. Nasal sprays for the treatment of migraine. Headache 2013; 53(3): 577-8.
[http://dx.doi.org/10.1111/head.12045] [PMID: 23489220]
[3]
Taylor D, Radbruch L, Revnic J, Torres LM, Ellershaw JE, Perelman M. A Report on the Long-Term Use of Fentanyl Pectin Nasal Spray in Patients With Recurrent Breakthrough Pain J Pain Symptom. Manage 2013; 47(6): 1001-7.
[4]
Laube BL. Devices for aerosol delivery to treat sinusitis. J Aerosol Med 2007; 20(Suppl. 1): S5-S17.
[PMID: 17411406]
[5]
Aggarwal R, Cardozo A, Homer JJ. The assessment of topical nasal drug distribution. Clin Otolaryngol Allied Sci 2004; 29(3): 201-5.
[http://dx.doi.org/10.1111/j.1365-2273.2004.00797.x] [PMID: 15142061]
[6]
Djupesland PG. Nasal drug delivery devices: characteristics and performance in a clinical perspective-a review. Drug Deliv Transl Res 2013; 3(1): 42-62.
[http://dx.doi.org/10.1007/s13346-012-0108-9] [PMID: 23316447]
[7]
Miyake MM, Bleier BS. The blood-brain barrier and nasal drug delivery to the central nervous system. Am J Rhinol Allergy 2015; 29(2): 124-7.
[http://dx.doi.org/10.2500/ajra.2015.29.4149] [PMID: 25785753]
[8]
Quintana DS, Westlye LT, Rustan ØG, et al. Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment. Transl Psychiatry 2015; 5(7): e602-2.
[http://dx.doi.org/10.1038/tp.2015.93] [PMID: 26171983]
[9]
Bahadur S, Pathak K. Physicochemical and physiological considerations for efficient nose-to-brain targeting. Expert Opin Drug Deliv 2012; 9(1): 19-31.
[http://dx.doi.org/10.1517/17425247.2012.636801] [PMID: 22171740]
[10]
Agrawal M, Saraf S, Saraf S, Antimisiaris SG, Chougule MB, Shoyele SA, et al. Nose-to-brain drug delivery: An update on clinical challenges and progress towards approval of anti-Alzheimer drugs. J Control Release 2018; 281: 139-77.
[http://dx.doi.org/10.1016/j.jconrel.2018.05.011]
[11]
Dhuria SV, Hanson LR, Frey WH II. Intranasal delivery to the central nervous system: mechanisms and experimental considerations. J Pharm Sci 2010; 99(4): 1654-73.
[http://dx.doi.org/10.1002/jps.21924] [PMID: 19877171]
[12]
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.
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.v21.i1.20] [PMID: 15099184]
[13]
Li BV, Jin F, Lee SL, et al. Bioequivalence for locally acting nasal spray and nasal aerosol products: standard development and generic approval. AAPS J 2013; 15(3): 875-83.
[http://dx.doi.org/10.1208/s12248-013-9494-2] [PMID: 23686396]
[14]
U.S. Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research D of DI (HFD-240). Draft: Guidance for Industry Bioavailability and Bioequivalence Studies for Nasal Aerosol and Nasal Sprays for Local Action 2003. Available from: http://www.fda.gov/cder/guidance/index.htm
[15]
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.
[http://dx.doi.org/10.1007/s11095-009-0002-4] [PMID: 19902337]
[16]
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.
[http://dx.doi.org/10.1007/s11095-011-0417-6] [PMID: 21499839]
[17]
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.
[http://dx.doi.org/10.1177/0194599811427519] [PMID: 22049020]
[18]
Sommer F, Kroger R, Lindemann J. Numerical simulation of humidification and heating during inspiration within an adult nose. Rhinology 2012; 50(2): 157-64.
[PMID: 22616076]
[19]
Inthavong K, Fung MC, Yang W, Tu J. Measurements of droplet size distribution and analysis of nasal spray atomization from different actuation pressure. J Aerosol Med Pulm Drug Deliv 2015; 28(1): 59-67.
[http://dx.doi.org/10.1089/jamp.2013.1093] [PMID: 24914675]
[20]
Inthavong K, Tian ZF, Li HF, Tu J, Yang W, Xue CL, et al. A numerical study of spray particle deposition in a human nasal cavity. Aerosol Sci Technol 2006; 40(11): 1034-45.
[http://dx.doi.org/10.1080/02786820600924978]
[21]
Everard ML. Inhalation therapy for infants. Adv Drug Deliv Rev 2003; 55(7): 869-78.
[http://dx.doi.org/10.1016/S0169-409X(03)00082-6] [PMID: 12842605]
[22]
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.
[http://dx.doi.org/10.1007/s10439-012-0603-7] [PMID: 22660850]
[23]
Carrigy NB, Ruzycki CA, Golshahi L, Finlay WH. Pediatric in vitro and in silico models of deposition via oral and nasal inhalation. J Aerosol Med Pulm Drug Deliv 2014; 27(3): 149-69.
[http://dx.doi.org/10.1089/jamp.2013.1075] [PMID: 24870701]
[24]
Cheng YS. Mechanisms of pharmaceutical aerosol deposition in the respiratory tract. AAPS PharmSciTech 2014; 15(3): 630-40.
[http://dx.doi.org/10.1208/s12249-014-0092-0] [PMID: 24563174]
[25]
Kleinstreuer C, Zhang Z, Donohue JF. Targeted drug-aerosol delivery in the human respiratory system. Annu Rev Biomed Eng 2008; 10(1): 195-220.
[http://dx.doi.org/10.1146/annurev.bioeng.10.061807.160544] [PMID: 18412536]
[26]
Vidgren MT, Kublik H. Nasal delivery systems and their effect on deposition and absorption. Adv Drug Deliv Rev 1998; 29(1-2): 157-77.
[http://dx.doi.org/10.1016/S0169-409X(97)00067-7] [PMID: 10837586]
[27]
Sahin-Yilmaz A, Naclerio RM. Anatomy and physiology of the upper airway. Proc Am Thorac Soc 2011; 8(1): 31-9.
[http://dx.doi.org/10.1513/pats.201007-050RN] [PMID: 21364219]
[28]
Anatomical GS, Drug HFAI, Delivery V. Curr Drug Deliv 2012; 9(6): 566-82.
[http://dx.doi.org/10.2174/156720112803529828] [PMID: 22788696]
[29]
Cole P. The four components of the nasal valve. Am J Rhinol 2003; 17(2): 107-10.
[http://dx.doi.org/10.1177/194589240301700208] [PMID: 12751706]
[30]
Yu S, Liu Y, Sun X, Li S. Influence of nasal structure on the distribution of airflow in nasal cavity. Rhinology 2008; 46(2): 137-43.
[PMID: 18575016]
[31]
Wilson WR, Allansmith MR. Rapid, atraumatic method for obtaining nasal mucus samples. Ann Otol Rhinol Laryngol 1976; 85(3 pt 1): 391-3.
[http://dx.doi.org/10.1177/000348947608500311] [PMID: 937966]
[32]
Halama AR, Decreton S, Bijloos JM, Clement PA. Density of epithelial cells in the normal human nose and the paranasal sinus mucosa. A scanning electron microscopic study. Rhinology 1990; 28(1): 25-32.
[PMID: 2336523]
[33]
Waddell AN, Patel SK, Toma AG, Maw AR. Intranasal steroid sprays in the treatment of rhinitis: is one better than another? J Laryngol Otol 2003; 117(11): 843-5.
[http://dx.doi.org/10.1258/002221503322542818] [PMID: 14670141]
[34]
Illum L. Nasal drug delivery-possibilities, problems and solutions. J Control Release 2003; 87(1-3): 187-98.
[http://dx.doi.org/10.1016/S0168-3659(02)00363-2] [PMID: 12618035]
[35]
Johnson NJ, Hanson LR, Frey WH. Trigeminal pathways deliver a low molecular weight drug from the nose to the brain and orofacial structures. Mol Pharm 2010; 7(3): 884-93.
[http://dx.doi.org/10.1021/mp100029t] [PMID: 20420446]
[36]
Proctor D, Andersen I. The mucociliary systemThe nose: upper airway physiology and the atmospheric environment. Amsterdam: Elsevier Biomedical 1982; pp. 245-78.
[37]
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.
[http://dx.doi.org/10.1007/s11095-016-1896-2] [PMID: 26943943]
[38]
Suman JD, Laube BL, Dalby R. Validity of in vitro tests on aqueous spray pumps as surrogates for nasal deposition, absorption, and biologic response. J Aerosol Med 2006; 19(4): 510-21.
[http://dx.doi.org/10.1089/jam.2006.19.510] [PMID: 17196079]
[39]
Finlay WH. The Mechanics of Inhaled Pharmaceutical Aerosols. 2nd ed. Elsevier 2019.
[40]
Suman JD, Laube BL, Dalby R. Comparison of nasal deposition and clearance of aerosol generated by nebulizer and an aqueous spray pump. Pharm Res 1999; 16(10): 1648-52.
[http://dx.doi.org/10.1023/A:1011933410898] [PMID: 10554112]
[41]
Vaughan WC, Carvalho G. Use of nebulized antibiotics for acute infections in chronic sinusitis. Otolaryngol Head Neck Surg 2002; 127(6): 558-68.
[http://dx.doi.org/10.1067/mhn.2002.129738] [PMID: 12501108]
[42]
Djupesland PG, Skretting A, Winderen M, Holand T. Bi-directional nasal delivery of aerosols can prevent lung deposition. J Aerosol Med 2004; 17(3): 249-59.
[http://dx.doi.org/10.1089/jam.2004.17.249] [PMID: 15625817]
[43]
Xi J, Wang Z, Nevorski D, White T, Zhou Y. Nasal and Olfactory Deposition with Normal and Bidirectional Intranasal Delivery Techniques: In Vitro Tests and Numerical Simulations. J Aerosol Med Pulm Drug Deliv 2017; 30(2): 118-31.
[http://dx.doi.org/10.1089/jamp.2016.1295] [PMID: 27977306]
[44]
Lelong N, Junqua-Moullet A, Diot P, Vecellio L. Comparison of laser diffraction measurements by Mastersizer X and Spraytec to characterize droplet size distribution of medical liquid aerosols. J Aerosol Med Pulm Drug Deliv 2014; 27(2): 94-102.
[http://dx.doi.org/10.1089/jamp.2012.1030] [PMID: 23668547]
[45]
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.
[http://dx.doi.org/10.1002/jps.20090] [PMID: 15176062]
[46]
Pozzoli M, Rogueda P, Zhu B, et al. Dry powder nasal drug delivery: challenges, opportunities and a study of the commercial Teijin Puvlizer Rhinocort device and formulation. Drug Dev Ind Pharm 2016; 42(10): 1660-8.
[http://dx.doi.org/10.3109/03639045.2016.1160110] [PMID: 26953090]
[47]
Guo C, Stine KJ, Kauffman JF, Doub WH. Assessment of the influence factors on in vitro testing of nasal sprays using Box-Behnken experimental design. Eur J Pharm Sci 2008; 35(5): 417-26.
[http://dx.doi.org/10.1016/j.ejps.2008.09.001] [PMID: 18832029]
[48]
Inthavong K, Yang W, Fung MC, Tu JY. External and near-nozzle spray characteristics of a continuous spray atomized from a nasal spray device. Aerosol Sci Technol 2012; 46(2): 165-77.
[http://dx.doi.org/10.1080/02786826.2011.617793]
[49]
Doughty DV, Vibbert C, Kewalramani A, Bollinger ME, Dalby RN. Automated actuation of nasal spray products: determination and comparison of adult and pediatric settings. Drug Dev Ind Pharm 2011; 37(3): 359-66.
[http://dx.doi.org/10.3109/03639045.2010.520321] [PMID: 20923391]
[50]
Inthavong K, Fung MC, Tong X, Yang W, Tu J. High resolution visualization and analysis of nasal spray drug delivery. Pharm Res 2014; 31(8): 1930-7.
[http://dx.doi.org/10.1007/s11095-013-1294-y] [PMID: 24549819]
[51]
Mygind N, Vesterhauge S. Aerosol distribution in the nose. Rhinology 1978; 16(2): 79-88.
[PMID: 684327]
[52]
Hallworth GW, Padfield JM. A comparison of the regional deposition in a model nose of a drug discharged from metered aerosol and metered-pump nasal delivery systems. J Allergy Clin Immunol 1986; 77(2): 348-53.
[http://dx.doi.org/10.1016/S0091-6749(86)80116-6] [PMID: 3944385]
[53]
Cheng YS, Holmes TD, Gao J, 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.
[http://dx.doi.org/10.1089/08942680152484199] [PMID: 11681658]
[54]
Shah SA, Dickens CJ, Ward DJ, Banaszek AA, George C, Horodnik W. Design of experiments to optimize an in vitro cast to predict human nasal drug deposition. J Aerosol Med Pulm Drug Deliv 2014; 27(1): 21-9.
[http://dx.doi.org/10.1089/jamp.2012.1011] [PMID: 23461532]
[55]
Foo MY, Cheng Y-S, Su W-C, Donovan MD. The influence of spray properties on intranasal deposition. J Aerosol Med 2007; 20(4): 495-508.
[http://dx.doi.org/10.1089/jam.2007.0638] [PMID: 18158721]
[56]
Guilmette RA, Wicks JD, Wolff RK. Morphometry of Human Nasal Airways In Vivo Using Magnetic Resonance Imaging. J Aerosol Med 2009; 2(4): 365-77.
[http://dx.doi.org/10.1089/jam.1989.2.365]
[57]
Guilmette RA, Gagliano TJ. Construction of a Model of Human Nasal Airways Using In Vivo Morphometric Data. Ann Occup Hyg 1994; 38: 69-75.
[58]
Xi J, Si XA, Gaide R. Electrophoretic particle guidance significantly enhances olfactory drug delivery: a feasibility study. PLoS One 2014; 9(1)e86593
[http://dx.doi.org/10.1371/journal.pone.0086593] [PMID: 24497957]
[59]
Swift DL, Montassier N, Hopke PK, Karpen-Hayes K, Cheng Y-S. Inspiratory deposition of ultrafine particles in human nasal replicate cast. J Aerosol Sci 1992; 23(1): 65-72.
[60]
Newman SP, Morén F, Clarke SW. Deposition pattern of nasal sprays in man. Rhinology 1988; 26(2): 111-20.
[PMID: 3175455]
[61]
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.
[http://dx.doi.org/10.1007/s11095-005-7391-9] [PMID: 16091994]
[62]
Kimbell JS, Segal RA, Asgharian B, et al. Characterization 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.
[http://dx.doi.org/10.1089/jam.2006.0531] [PMID: 17388754]
[63]
Kelly JT, Asgharian B, Kimbell JS, Wong BA. Particle Deposition in Human Nasal Airway Replicas Manufactured by Different Methods. Part I: Inertial Regime Particles. Aerosol Sci Technol 2011; 38(11): 1063-71.
[http://dx.doi.org/10.1080/027868290883360]
[64]
Schroeter JD, Tewksbury EW, Wong BA, Kimbell JS. Experimental measurements and computational predictions of regional particle deposition in a sectional nasal model. J Aerosol Med Pulm Drug Deliv 2015; 28(1): 20-9.
[http://dx.doi.org/10.1089/jamp.2013.1084] [PMID: 24580111]
[65]
Hughes R, Watterson J, Dickens C, Ward D, Banaszek A. Development of a nasal cast model to test medicinal nasal devices. Proc Inst Mech Eng H 2008; 222(7): 1013-22.
[http://dx.doi.org/10.1243/09544119JEIM423] [PMID: 19024150]
[66]
Shah SA, George C, Berger R, Gupta P, Wan J, Connor A, et al. In Vivo Nasal Deposition from Different Delivery Devices and Formulations. In: International Pharmaceutical Aerosol Consortium on Regulation & Science Conference 2011; p. 2.
[67]
Ruzycki CA, Yang M, Chan H-K, Finlay WH. Improved prediction of intersubject variability in extrathoracic aerosol deposition using algebraic correlations. Aerosol Sci Technol 2017; 51(6): 667-73.
[http://dx.doi.org/10.1080/02786826.2017.1306640]
[68]
Liu Y, Johnson MR, Matida EA, Kherani S, Marsan J. Creation of a standardized geometry of the human nasal cavity. J Appl Physiol (1985) 2009; 106(3): 784-95.
[http://dx.doi.org/10.1152/japplphysiol.90376.2008] [PMID: 19131483]
[69]
Kiaee M, Wachtel H, Noga ML, Martin AR, Finlay WH. An idealized geometry that mimics average nasal spray deposition in adults: A computational study. Comput Biol Med 2019; 107: 206-17.
[http://dx.doi.org/10.1016/j.compbiomed.2019.02.013] [PMID: 30851506]
[70]
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.
[http://dx.doi.org/10.1080/02786826.2014.931566]
[71]
Warnken ZN, Smyth HDC, Davis DA, Weitman S, Kuhn JG, Williams RO III. 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; 15(4): 1392-402.
[http://dx.doi.org/10.1021/acs.molpharmaceut.7b00702] [PMID: 29485888]
[72]
Laube BL, Sharpless G, Vikani AR, 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.
[http://dx.doi.org/10.1089/jamp.2014.1174] [PMID: 25679810]
[73]
Sawant N, Donovan MD. In vitro assessment of spray deposition patterns in a pediatric (12 year-old) nasal cavity model. 2018; 35(5): 1-2.
[74]
Tu J, Inthavong K, Ahmadi G. Fundamentals of Fluid Dynamics BT - Computational Fluid and Particle Dynamics in the Human Respiratory System. Dordrecht: Springer Netherlands 2013; pp. 101-38.
[75]
Cole P. Nasal and oral airflow resistors. Site, function, and assessment. Arch Otolaryngol Head Neck Surg 1992; 118(8): 790-3.http://www.ncbi.nlm.nih.gov/pubmed/1642827
[http://dx.doi.org/10.1001/archotol.1992.01880080012004] [PMID: 1642827]
[76]
Fodil R, Brugel-Ribere L, Croce C, et al. Inspiratory flow in the nose: a model coupling flow and vasoerectile tissue distensibility. J Appl Physiol (1985) 2005; 98(1): 288-95.http://www.ncbi.nlm.nih.gov/pubmed/15333615
[http://dx.doi.org/10.1152/japplphysiol.00625.2004] [PMID: 15333615]
[77]
Liu Y, Matida EA, Johnson MR. Experimental measurements and computational modeling of aerosol deposition in the Carleton-Civic standardized human nasal cavity. J Aerosol Sci 2010; 41(6): 569-86.
[http://dx.doi.org/10.1016/j.jaerosci.2010.02.014]
[78]
Shi H. Numerical simulation of airflow, particle deposition and drug delivery in a representative human nasal airway model. ProQuest Diss Theses 2006; p. 202.
[79]
Shi H, Kleinstreuer C, Zhang Z. Modeling of inertial particle transport and deposition in human nasal cavities with wall roughness. J Aerosol Sci 2007; 38(4): 398-419.
[http://dx.doi.org/10.1016/j.jaerosci.2007.02.002]
[80]
Keyhani K, Scherer PW, Mozell MM. Numerical simulation of airflow in the human nasal cavity. J Biomech Eng 1995; 117(4): 429-41.
[http://dx.doi.org/10.1115/1.2794204] [PMID: 8748525]
[81]
Tarabichi M, Fanous N. Finite element analysis of airflow in the nasal valve. Arch Otolaryngol Head Neck Surg 1993; 119(6): 638-42.
[http://dx.doi.org/10.1001/archotol.1993.01880180054010] [PMID: 8499094]
[82]
Elad D, Liebenthal R, Wenig BL, Einav S. Analysis of air flow patterns in the human nose. Med Biol Eng Comput 1993; 31(6): 585-92.
[http://dx.doi.org/10.1007/BF02441806] [PMID: 8145584]
[83]
Subramaniam RP, Richardson RB, Morgan KT, Kimbell JS, Guilmette RA. Computational Fluid Dynamics Simulations of Inspiratory Airflow in the Human Nose and Nasopharynx. Inhal Toxicol 2002; 10(2): 91-120.
[http://dx.doi.org/10.1080/089583798197772]
[84]
Schroeter JD, Kimbell JS, Asgharian B. Analysis of particle deposition in the turbinate and olfactory regions using a human nasal computational fluid dynamics model. J Aerosol Med 2006; 19(3): 301-13.
[http://dx.doi.org/10.1089/jam.2006.19.301] [PMID: 17034306]
[85]
Inthavong K, Tian ZF, Tu JY, Yang W, Xue C. Optimising nasal spray parameters for efficient drug delivery using computational fluid dynamics. Comput Biol Med 2008; 38(6): 713-26.
[http://dx.doi.org/10.1016/j.compbiomed.2008.03.008] [PMID: 18468593]
[86]
Inthavong K, Ge Q, Se CMK, Yang W, Tu JY. Simulation of sprayed particle deposition in a human nasal cavity including a nasal spray device. J Aerosol Sci 2010; 42(2): 100-13.
[http://dx.doi.org/10.1016/j.jaerosci.2010.11.008]
[87]
Tong X, Dong J, Shang Y, Inthavong K, Tu J. Effects of nasal drug delivery device and its orientation on sprayed particle deposition in a realistic human nasal cavity. Comput Biol Med 2016; 77: 40-8.
[http://dx.doi.org/10.1016/j.compbiomed.2016.08.002]
[88]
Kiaee M, Wachtel H, Noga ML, Martin AR, Finlay WH. Regional deposition of nasal sprays in adults: A wide ranging computational study. Int J Numer Methods Biomed Eng 2018; 34(5)e2968
[http://dx.doi.org/10.1002/cnm.2968] [PMID: 29453801]
[89]
Chen XB, Lee HP, Chong VFH, Wang Y. A computational fluid dynamics model for drug delivery in a nasal cavity with inferior turbinate hypertrophy. J Aerosol Med Pulm Drug Deliv 2010; 23(5): 329-38.
[http://dx.doi.org/10.1089/jamp.2009.0776] [PMID: 20804427]
[90]
Frank DO, Kimbell JS, Cannon D, Pawar SS, Rhee JS. Deviated nasal septum hinders intranasal sprays: a computer simulation study. Rhinology 2012; 50(3): 311-8.
[http://dx.doi.org/10.4193/Rhin12.053] [PMID: 22888490]
[91]
Frank DO, Kimbell JS, Cannon D, Rhee JS. Computed intranasal spray penetration: comparisons before and after nasal surgery. Int Forum Allergy Rhinol 2013; 3(1): 48-55.
[http://dx.doi.org/10.1002/alr.21070] [PMID: 22927179]
[92]
Fung MC, Inthanvong K, Yang W, Tu J. Experimental and numerical modelling of nasal spray atomisation. Ninth Int Conf CFD Miner Process Ind. 1-6.
[93]
Engelhardt L, Röhm M, Mavoungou C, Schindowski K, Schafmeister A, Simon U. First Steps to Develop and Validate a CFPD Model in Order to Support the Design of Nose-to-Brain Delivered Biopharmaceuticals. Pharm Res 2016; 33(6): 1337-50.
[http://dx.doi.org/10.1007/s11095-016-1875-7] [PMID: 26887679]
[94]
Kleven M, Melaaen MC, Reimers M, Røtnes JS, Aurdal L, Djupesland PG. Using Computational Fluid Dynamics (CFD) to Improve the Bi-Directional Nasal Drug Delivery Concept. Food Bioprod Process 2005; 83(2): 107-17.
[http://dx.doi.org/10.1205/fbp.04403]
[95]
Xi J, Yuan JE, Si XA, Hasbany J. Numerical optimization of targeted delivery of charged nanoparticles to the ostiomeatal complex for treatment of rhinosinusitis. Int J Nanomedicine 2015; 10: 4847-61.
[http://dx.doi.org/10.2147/IJN.S87382] [PMID: 26257521]
[96]
Xi J, Yuan JE, Alshaiba M, et al. Design and Testing of Electric- Guided Delivery of Charged Particles to the Olfactory Region: Experimental and Numerical Studies. Curr Drug Deliv 2016; 13(2): 265-74.http://www.eurekaselect.com/openurl/content.php?genre=article&issn=1567-2018&volume=13&issue=2&spage=265 [Internet].
[http://dx.doi.org/10.2174/1567201812666150909093050] [PMID: 26362143]
[97]
Xi J, Zhang Z, Si XA. Improving intranasal delivery of neurological nanomedicine to the olfactory region using magnetophoretic guidance of microsphere carriers. Int J Nanomedicine 2015; 10: 1211-22.
[http://dx.doi.org/10.2147/IJN.S77520] [PMID: 25709443]
[98]
Si XA, Xi J. Modeling and Simulations of Olfactory Drug Delivery with Passive and Active Controls of Nasally Inhaled Pharmaceutical Aerosols. J Vis Exp 2016; (111): 1-9.
[http://dx.doi.org/10.3791/53902] [PMID: 27285852]
[99]
Foo MY, Sawant N, Overholtzer E, Donovan MD. A Simplified Geometric Model to Predict Nasal Spray Deposition in Children and Adults. AAPS PharmSciTech 2018; 19(7): 2767-77.
[http://dx.doi.org/10.1208/s12249-018-1031-2] [PMID: 29948982]

Rights & Permissions Print Cite
Article Metrics
16
1
© 2024 Bentham Science Publishers | Privacy Policy