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Omar S Usmani - One of the best experts on this subject based on the ideXlab platform.
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pulmonary deposition of budesonide glycopyrronium formoterol fumarate dihydrate metered dose inhaler formulated using co suspension delivery technology in healthy male subjects
European Journal of Pharmaceutical Sciences, 2020Co-Authors: Samuel Israel, Ashish Kumar, Kiernan Deangelis, Magnus Aurivillius, Paul Dorinsky, Nicolas Roche, Omar S UsmaniAbstract:Abstract This Gamma Scintigraphy imaging study assessed pulmonary, extrathoracic and regional lung deposition patterns of a radiolabelled inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2-agonist triple fixed-dose combination budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF 320/14.4/10 μg), delivered by pressurised metered dose inhaler (pMDI) using innovative co-suspension delivery technology (Aerosphere™). In this Phase I, randomised, single-centre, single-dose, two-period, crossover study (NCT03740373), 10 healthy male adults received two actuations of BGF MDI (160/7.2/4.8 μg per actuation) radiolabelled with 99mTc, not exceeding 5 MBq per actuation. Immediately following each inhalation, subjects performed a 10- or 3-second breath-hold, then exhaled into an exhalation filter. The primary objective was to assess the pulmonary deposition of BGF MDI following the 10-second breath-hold. The secondary objectives were to assess deposition after the 3-second breath-hold and lung regional and extrathoracic deposition after each breath-hold length. Imaging of the lungs, stomach, head and neck was recorded by Gamma Scintigraphy immediately after exhalation. The mean BGF MDI emitted dose deposited in the lungs was 37.7% for the 10-second breath-hold and 34.5% for the 3-second breath-hold. Emitted dose detected in the exhalation filter was ≤0.4% for both breath-hold lengths. The mean normalised peripheral/central ratio was 0.65 and 0.75 for the 10- and 3-second breath-holds, respectively, while the standardised central/peripheral ratios were 1.79 and 1.40, respectively. There were no new or unexpected safety findings. In conclusion, BGF MDI was efficiently deposited in the central and the peripheral regions of the lungs, with similar regional deposition patterns following a 10- and 3-second breath-hold.
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comparing lung geometrical areas of interest in Gamma Scintigraphy as assessment tool for inhaled drug deposition
European Respiratory Journal, 2018Co-Authors: Abdullah Ghazwani, Martyn F Biddiscombe, Omar S UsmaniAbstract:Background: Planar Gamma Scintigraphy is a powerful tool in therapeutic aerosol studies to evaluate inhaled drug delivery to the lungs. Alas, different laboratories use different approaches for analysing and quantifying aerosol lung deposition and its airway distribution, making it difficult to compare data. Aim: To compare the most common analysis approaches, assess total and regional deposition of inhaled aerosol and highlight similarities and differences. The eventually aim is to draw nearer to a consensus on standardized methodology for defining lung regions of interest so that data from different laboratories may be compared. Method: The six most frequently reported methods in the literature to define lung regions of interest were compared. The primary index to evaluate differences between the six methods was penetration index (PI); a measure of regional lung distribution expressed as the central to peripheral deposition ratio for inhaled therapeutic aerosols normalised by the same ratio for a Krypton gas scan. Data from 12 mild asthmatic patients (FEV1=86. %pred) inhaling monodisperse albuterol aerosols of particle size 1.5, 3, and 6 µm(total of 47 Gamma Scintigraphy images each to be analysed by 6 methods) were analysed using the HERMES Nuclear Medicine data analysis software (Hermes Medical Solutions, Stockholm, Sweden). Results: PI values were generated for the three droplet sizes of aerosol (1.5, 3 and 6 µm) in all subjects in all methods. PI values show greater variability between methods 1, 2, and 4, but were more consistent between methods 3, 5, and 6.
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Gamma scintigraphic pulmonary deposition study of glycopyrronium formoterol metered dose inhaler formulated using co suspension delivery technology
European Journal of Pharmaceutical Sciences, 2018Co-Authors: Glyn Taylor, Simon Warren, Sarvajna Kumar Dwivedi, Mark Sommerville, Lauren Mello, Chad Orevillo, Andrea Maes, Ubaldo J Martin, Omar S UsmaniAbstract:Abstract This Gamma Scintigraphy imaging study was the first to assess pulmonary and extrathoracic deposition and regional lung deposition patterns of a radiolabelled long-acting muscarinic antagonist/long-acting β 2 -agonist fixed-dose combination glycopyrronium/formoterol fumarate dihydrate (GFF) 14.4/10 μg (equivalent to glycopyrrolate/formoterol fumarate 18/9.6 μg), delivered by pressurized metered dose inhaler (pMDI) using novel co-suspension delivery technology. In this Phase I, randomized, single-centre, single-blind, single-dose, two-treatment, crossover, placebo-controlled study (PT003020), 10 healthy male adults received two actuations of GFF pMDI (7.2/5.0 μg per actuation) and placebo pMDI (containing phospholipid-based porous particles without active pharmaceutical ingredient), both radiolabelled with 99m Tc, up to 5 MBq per actuation. Gamma Scintigraphy images of lungs, stomach, head and neck were recorded. In addition, images of the actuators after use, collected mouth washings and exhalation filters were acquired. On average, 38.4% of the emitted dose of radiolabelled GFF pMDI, and 32.8% of radiolabelled placebo pMDI, was deposited in the lungs. The percentage emitted dose detected in the oropharyngeal and stomach regions was 61.4% and 66.9% for radiolabelled GFF pMDI and placebo pMDI, respectively. For both treatments, ≤ 0.25% of the emitted dose was detected in the exhalation filter. The normalized outer/inner ratio was 0.57 and 0.59 for radiolabelled GFF pMDI and placebo pMDI, respectively, and the standardized central/peripheral ratio was 1.85 and 1.94 respectively, indicating delivery of both co-suspension delivery technology formulations throughout the airways. There were no new or unexpected safety findings. In conclusion, both formulations were efficiently and uniformly deposited in the lungs with similar regional deposition patterns, oropharyngeal and stomach deposition, exhalation fraction and actuator-recovered dose.
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comparing lung regions of interest in Gamma Scintigraphy for assessing inhaled therapeutic aerosol deposition
Journal of Aerosol Medicine and Pulmonary Drug Delivery, 2011Co-Authors: Martyn F Biddiscombe, Sally Meah, Richard S Underwood, Omar S UsmaniAbstract:Abstract Background: Two-dimensional Gamma Scintigraphy is an important technique used to evaluate the lung deposition from inhaled therapeutic aerosols. Images are divided into regions of interest and deposition indices are derived to quantify aerosol distribution within the intrapulmonary airways. In this article, we compared the different approaches that have been historically used between different laboratories for geometrically defining lung regions of interest. We evaluated the effect of these different approaches on the derived indices classically used to assess inhaled aerosol deposition in the lungs. Our primary intention was to assess the ability of different regional lung templates to discriminate between central and peripheral airway deposition patterns generated by inhaling aerosols of different particle sizes. Methods: We investigated six methods most commonly reported in the scientific literature to define lung regions of interest and assessed how different each of the derived regional lung...
William D Bennett - One of the best experts on this subject based on the ideXlab platform.
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validation of sinus drug delivery computational fluid dynamics cfd modeling with in vitro Gamma Scintigraphy
arXiv: Medical Physics, 2020Co-Authors: Kathryn Kudlaty, William D Bennett, Landon T Holbrook, Alyssa Burke, Benjamin Langworthy, Jason P Fine, Charles S Ebert, Adam J Kimple, Brian D Thorp, Adam M ZanationAbstract:Background: Chronic rhinosinusitis (CRS) is a prevalent and disruptive disease. Medical management including nasal steroid sprays is the primary treatment modality. Computational fluid dynamics (CFD) has been used to characterize sinonasal airflow and intranasal drug delivery; however, variation in simulation methods indicates a need for large scale CFD model validation. Methods: Anatomic reconstructions of pre and post-operative CT scans of 3 functional endoscopic sinus surgery patients were created in Mimics(TM). Fluid analysis and drug particle deposition modeling were conducted using CFD methods with Fluent(TM) in 18 cases. Models were 3D printed and in vitro studies were performed using Tc99-labeled Nasacort(TM). Gamma Scintigraphy signals and CFD-modeled spray mass were post-processed in a superimposed grid and compared. Statistical analysis using overlap coefficients (OCs) evaluated similarities between computational and experimental distributions and Kendall's tau rank correlation coefficient was employed to test independence. Results: OCs revealed strong agreement in percent deposition and grid profiles between CFD models and experimental results (mean [range] for sagittal, axial, and coronal grids were 0.69 [0.57], 0.61 [0.49], and 0.78 [0.44], respectively). Kendall's tau values showed strong agreement (average 0.73) between distributions, which were statistically significant (p < 0.05) apart from a single coronal grid in one model and two sagittal grids of another. Conclusions: CFD modeling demonstrates statistical agreement with in vitro experimental results. This validation study is one of the largest of its kind and supports the applicability of CFD in accurately modeling nasal spray drug delivery and using computational methods to investigate means of improving clinical drug delivery.
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homogeneity of aerosol deposition and mucociliary clearance are improved following ivacaftor treatment in cystic fibrosis
Journal of Aerosol Medicine and Pulmonary Drug Delivery, 2017Co-Authors: William D Bennett, Kirby L Zeman, Beth L Laube, Gail Sharpless, Peter J Mogayzel, Scott H DonaldsonAbstract:Abstract Background: Using planar Gamma Scintigraphy of inhaled radioaerosols, we have developed new analytical methods for assessing homogeneity of aerosol deposition and time-dependent particle c...
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regional ventilation is the main determinant of alveolar deposition of coarse particles in the supine healthy human lung during tidal breathing
Journal of Aerosol Medicine and Pulmonary Drug Delivery, 2017Co-Authors: Kirby L Zeman, William D Bennett, Kim G Prisk, Chantal DarquenneAbstract:Abstract Background: To quantify the relationship between regional lung ventilation and coarse aerosol deposition in the supine healthy human lung, we used oxygen-enhanced magnetic resonance imaging and planar Gamma Scintigraphy in seven subjects. Methods: Regional ventilation was measured in the supine posture in a 15 mm sagittal slice of the right lung. Deposition was measured by using planar Gamma Scintigraphy (coronal scans, 40 cm FOV) immediately postdeposition, 1 hour 30 minutes and 22 hours after deposition of 99mTc-labeled particles (4.9 μm MMAD, GSD 2.5), inhaled in the supine posture (flow 0.5 L/s, 15 breaths/min). The distribution of retained particles at different times was used to infer deposition in different airway regions, with 22 hours representing alveolar deposition. The fraction of total slice ventilation per quartile of lung height from the lung apex to the dome of the diaphragm at functional residual capacity was computed, and co-registered with deposition data—apices aligned—using a...
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heterogeneity of particle deposition by pixel analysis of 2d Gamma Scintigraphy images
Journal of Aerosol Medicine and Pulmonary Drug Delivery, 2014Co-Authors: William D Bennett, Miao Xie, Kirby L Zeman, Harry L Hurd, Scott H DonaldsonAbstract:Abstract Background: Heterogeneity of inhaled particle deposition in airways disease may be a sensitive indicator of physiologic changes in the lungs. Using planar Gamma Scintigraphy, we developed new methods to locate and quantify regions of high (hot) and low (cold) particle deposition in the lungs. Methods: Initial deposition and 24 hour retention images were obtained from healthy (n=31) adult subjects and patients with mild cystic fibrosis lung disease (CF) (n=14) following inhalation of radiolabeled particles (Tc99m-sulfur colloid, 5.4 μm MMAD) under controlled breathing conditions. The initial deposition image of the right lung was normalized to (i.e., same median pixel value), and then divided by, a transmission (Tc99m) image in the same individual to obtain a pixel-by-pixel ratio image. Hot spots were defined where pixel values in the deposition image were greater than 2X those of the transmission, and cold spots as pixels where the deposition image was less than 0.5X of the transmission. The numb...
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comparison of 133xenon ventilation equilibrium scan xv and 99mtechnetium transmission tt scan for use in regional lung analysis by 2d Gamma Scintigraphy in healthy and cystic fibrosis lungs
Journal of Aerosol Medicine and Pulmonary Drug Delivery, 2013Co-Authors: Kirby L Zeman, Scott H Donaldson, William D BennettAbstract:Abstract Background: Quantification of particle deposition in the lung by Gamma Scintigraphy requires a reference image for location of regions of interest (ROIs) and normalization to lung thickness. In various laboratories, the reference image is made by a transmission scan (57Co or 99mTc) or gas ventilation scan (133Xe or 81Kr). There has not been a direct comparison of measures from the two methods. Methods: We compared 99mTc transmission scans to 133Xe equilibrium ventilation scans as reference images for 38 healthy subjects and 14 cystic fibrosis (CF) patients for their effects on measures of regional particle deposition: the central-to-peripheral ratio of lung counts (C/P); and ROI area versus forced vital capacity. Whole right lung ROI was based on either an isocontour threshold of three times the soft tissue transmission (TT) or a threshold of 20% of peak xenon ventilation counts (XV). We used a central ROI drawn to 50% of height and of width of the whole right lung ROI and placed along the left l...
Glyn Taylor - One of the best experts on this subject based on the ideXlab platform.
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Gamma scintigraphic pulmonary deposition study of glycopyrronium formoterol metered dose inhaler formulated using co suspension delivery technology
European Journal of Pharmaceutical Sciences, 2018Co-Authors: Glyn Taylor, Simon Warren, Sarvajna Kumar Dwivedi, Mark Sommerville, Lauren Mello, Chad Orevillo, Andrea Maes, Ubaldo J Martin, Omar S UsmaniAbstract:Abstract This Gamma Scintigraphy imaging study was the first to assess pulmonary and extrathoracic deposition and regional lung deposition patterns of a radiolabelled long-acting muscarinic antagonist/long-acting β 2 -agonist fixed-dose combination glycopyrronium/formoterol fumarate dihydrate (GFF) 14.4/10 μg (equivalent to glycopyrrolate/formoterol fumarate 18/9.6 μg), delivered by pressurized metered dose inhaler (pMDI) using novel co-suspension delivery technology. In this Phase I, randomized, single-centre, single-blind, single-dose, two-treatment, crossover, placebo-controlled study (PT003020), 10 healthy male adults received two actuations of GFF pMDI (7.2/5.0 μg per actuation) and placebo pMDI (containing phospholipid-based porous particles without active pharmaceutical ingredient), both radiolabelled with 99m Tc, up to 5 MBq per actuation. Gamma Scintigraphy images of lungs, stomach, head and neck were recorded. In addition, images of the actuators after use, collected mouth washings and exhalation filters were acquired. On average, 38.4% of the emitted dose of radiolabelled GFF pMDI, and 32.8% of radiolabelled placebo pMDI, was deposited in the lungs. The percentage emitted dose detected in the oropharyngeal and stomach regions was 61.4% and 66.9% for radiolabelled GFF pMDI and placebo pMDI, respectively. For both treatments, ≤ 0.25% of the emitted dose was detected in the exhalation filter. The normalized outer/inner ratio was 0.57 and 0.59 for radiolabelled GFF pMDI and placebo pMDI, respectively, and the standardized central/peripheral ratio was 1.85 and 1.94 respectively, indicating delivery of both co-suspension delivery technology formulations throughout the airways. There were no new or unexpected safety findings. In conclusion, both formulations were efficiently and uniformly deposited in the lungs with similar regional deposition patterns, oropharyngeal and stomach deposition, exhalation fraction and actuator-recovered dose.
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a Gamma Scintigraphy study to investigate lung deposition and clearance of inhaled amikacin loaded liposomes in healthy male volunteers
Journal of Aerosol Medicine and Pulmonary Drug Delivery, 2009Co-Authors: Jeffry G Weers, Glyn Taylor, Simon Warren, Beth Metzheiser, Paul Meers, Walter PerkinsAbstract:Background: The purpose of this study was to investigate the inhalation of a liposomal formulation of amikacin in healthy male volunteers in terms of pulmonary deposition, clearance, and safety following nebulization with a commercial jet nebulizer. Methods: Amikacin was encapsulated in liposomes comprised of dipalmitoyl phosphatidylcholine (DPPC) and cholesterol via a proprietary manufacturing process (20 mg/mL final amikacin concentration). The liposomes were radiolabeled with 99mTc using the tin chloride labeling method. A nominal dose of 120 mg of drug product was loaded into a PARI LC STAR nebulizer, aerosolized using a PARI Boy compressor where subjects inhaled for 20 min. Lung deposition was determined by Gamma Scintigraphy in three healthy male volunteers at the following time points (0, 1, 3, 6, 12, 24, 48, and 72 h post-administration). Results: Total lung deposition, expressed as a percentage of the emitted dose, was 32.3 � 3.4%. The time-dependent retention of radiolabeled liposomes was biphasic with an initial rapid reduction in counts, followed by a slower phase to 48 h. The overall mean retention at 24 and 48 h was 60.4 and 38.3% of the initial dose deposited, respectively. The observed clearance of radiolabel is consistent with clearance of amikacin following aerosol delivery to rats. There were no clinically significant changes in laboratory parameters, vital signs, or ECG. No adverse events including cough or bronchospasm were reported. Conclusions: Inhalation of a single nominal dose of 120 mg liposomal amikacin results in prolonged retention of drug-loaded liposomes in the lungs of healthy volunteers. The treatment was well tolerated.
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the pharmacokinetics of pulmonary delivered insulin a comparison of intratracheal and aerosol administration to the rabbit
Pharmaceutical Research, 1992Co-Authors: Paul Colthorpe, Glyn Taylor, Stephen J Farr, Lan J Smith, David WyattAbstract:The pulmonary deposition and pharmacokinetics of insulin, administered via an endotracheal tube as an aerosol and instillate, in formulations containing either 113mIn-DTPA or 99mTc-DTPA (for Gamma scintigraphic imaging) have been studied in four male New Zealand White rabbits. Using a randomized crossover design, the pharmacokinetics of intravenous insulin were also characterized. Recovery of immunoreactive insulin after nebulization was greater than 90%, indicating that the aerosolisation procedure did not cause appreciable insulin degradation. Gamma Scintigraphy demonstrated that the penetration index (peripheral:central deposition) for the aerosolized formulation (1.52) was much greater than that for the instillate (0.32). Gamma Scintigraphy also allowed exact quantification of the dose deposited after aerosol administration and thus permitted accurate determination of bioavailabilities. The bioavailable fraction for aerosolized insulin was 10-fold greater than for instilled insulin (57.2 vs 5.6%). Mucociliary clearance was likely to be greater for the instillate since it showed a preferential central deposition; this may account for the lower bioavailability. Insulin pharmacokinetics from both pulmonary formulations were absorption rate limited, resulting in postpeak half-lives which were approximately 20-fold greater than the intravenous elimination half-life (3 min). The apparent absorption rate constants resulting from instillation and aerosolisation were statistically equivalent (0.015 and 0.011 min−1, respectively). Mucociliary clearance of insulin would result in an overestimation of the true absorption rate constant; hence if mucociliary transport were greater for the instillate, then the true airways to blood transfer rate constant will be higher for the aerosolized formulation.
Ian R. Wilding - One of the best experts on this subject based on the ideXlab platform.
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in vivo disintegration profiles of encapsulated and nonencapsulated sumatriptan Gamma Scintigraphy in healthy volunteers
The Journal of Clinical Pharmacology, 2005Co-Authors: Ian R. Wilding, Darren Clark, Heather Wray, Jeff Alderman, Nancy Muirhead, Carolyn R SikesAbstract:The goal of this exploratory pilot study was to use Gamma Scintigraphy to evaluate, under physiological conditions, disintegration profiles of encapsulated and nonencapsulated formulations of 100 mg sumatriptan. Using a crossover design, healthy volunteers (n = 10) ingested 100-mg doses of sumatriptan tablets radiolabeled with 111Indium, as well as encapsulated sumatriptan tablets that were prepared similarly, then placed within a gelatin capsule and backfilled with an excipient blend radiolabeled with 99mTechnetium. A Gamma camera recorded scintigraphic images until 5 hours postdose. Initial disintegration of the gelatin capsule was observed at a mean (range) of 5 minutes (1-11 minutes); disintegration was complete within 14 minutes (5-24 minutes). For nonencapsulated versus encapsulated tablets, the mean (+/- standard deviation) time to initial disintegration (6 +/- 5 minutes vs 8 +/- 5 minutes) and time to complete disintegration (18 +/- 14 minutes vs 16 +/- 7 minutes) were comparable. Results of this study demonstrate that encapsulated and nonencapsulated sumatriptan have equivalent in vivo dissolution rates.
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bioequivalence testing for locally acting gastrointestinal products what role for Gamma Scintigraphy
The Journal of Clinical Pharmacology, 2002Co-Authors: Ian R. WildingAbstract:Bioequivalence testing for locally acting gastrointestinal products is a challenging issue for both the pharmaceutical industry and the global regulatory authorities. It is widely accepted that for medicinal products not intended to be delivered into the systemic circulation, pharmacokinetic bioavailability cannot be used. However, it is becoming increasingly accepted that local availability may be assessed, where appropriate, by approaches that qualitatively reflect the presence of the active substance at the site of action. These methods must be specifically chosen for that combination of active substance and route of drug delivery. This paper argues for the use of Gamma Scintigraphy as a validated measure of local availability and bioequivalence for topically acting products administered to the gastrointestinal tract by the oral and rectal route.
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A scintigraphic study to investigate the potential for altered gut distribution of loperamide from a loperamide-simethicone formulation in man.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2001Co-Authors: Alyson Connor, Heather Wray, J Cottrell, Ian R. WildingAbstract:A loperamide simethicone combination formulation has recently been demonstrated to have significant clinical advantages compared to loperamide alone in the relief of diarrhoea and related symptoms. The product visualisation technique of Gamma Scintigraphy has been used to investigate the interaction of the formulation with the heterogenous environment of the human gut in a group of 12 healthy volunteers. The results suggest that changes in the intestinal kinetics of loperamide from the combination product, e.g. jejunal coating, could be contributing to the improved efficacy.
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localization of drug release sites from an oral sustained release formulation of 5 asa pentasa in the gastrointestinal tract using Gamma Scintigraphy
The Journal of Clinical Pharmacology, 1993Co-Authors: J G Hardy, R A Sparrow, K P Steed, W J Harvey, G B Marshall, M Macarios, Ian R. WildingAbstract:Release of 5-ASA from a sustained release formulation (Pentasa, Ferring A/S, Copenhagen, Denmark) was monitored with plasma sampling for up to 24 hours in nine volunteers under both fasted and fed conditions. Drug absorption was correlated with location of the sustained-release microgranules in the gastrointestinal tract by Gamma Scintigraphy. Disintegration of the labeled tablet preparation occurred in the stomach within 20 minutes and acetylated 5-ASA was detectable in the plasma less than 60 minutes after ingestion. No significant differences were detected in either transit times through the small intestine, peak plasma acetylated 5-ASA concentration or lag time to absorption between fasted and fed individuals. Peak plasma concentration of acetylated 5-ASA usually occurred when the microgranules were present in the small intestine or ascending colon. The pharmacoscintigraphic study confirmed that 5-ASA release from the formulation occurred throughout the gastrointestinal tract, and that food effects on the in vivo behavior of the preparation were minimal.
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the effect of food on the in vivo behaviour of a novel sustained release formulation of tiaprofenic acid
International Journal of Pharmaceutics, 1992Co-Authors: Ian R. Wilding, S.s. Davis, R A Sparrow, J R Bloor, G Hayes, G T WardAbstract:Abstract A novel sustained release tablet formulation of tiaprofenic acid, that has been designed to disintegrate into discrete pellets in the gastrointestinal tract, has been evaluated using a combination of Gamma Scintigraphy and pharmacokinetics. The performance of the product in vivo was very satisfactory, in that the disintegration of the tableted pellet formulation was rapid. The gastrointestinal transit behaviour of pellets was affected by food, but food did not affect the subsequent absorption of the released drug.
Adam M Zanation - One of the best experts on this subject based on the ideXlab platform.
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validation of sinus drug delivery computational fluid dynamics cfd modeling with in vitro Gamma Scintigraphy
arXiv: Medical Physics, 2020Co-Authors: Kathryn Kudlaty, William D Bennett, Landon T Holbrook, Alyssa Burke, Benjamin Langworthy, Jason P Fine, Charles S Ebert, Adam J Kimple, Brian D Thorp, Adam M ZanationAbstract:Background: Chronic rhinosinusitis (CRS) is a prevalent and disruptive disease. Medical management including nasal steroid sprays is the primary treatment modality. Computational fluid dynamics (CFD) has been used to characterize sinonasal airflow and intranasal drug delivery; however, variation in simulation methods indicates a need for large scale CFD model validation. Methods: Anatomic reconstructions of pre and post-operative CT scans of 3 functional endoscopic sinus surgery patients were created in Mimics(TM). Fluid analysis and drug particle deposition modeling were conducted using CFD methods with Fluent(TM) in 18 cases. Models were 3D printed and in vitro studies were performed using Tc99-labeled Nasacort(TM). Gamma Scintigraphy signals and CFD-modeled spray mass were post-processed in a superimposed grid and compared. Statistical analysis using overlap coefficients (OCs) evaluated similarities between computational and experimental distributions and Kendall's tau rank correlation coefficient was employed to test independence. Results: OCs revealed strong agreement in percent deposition and grid profiles between CFD models and experimental results (mean [range] for sagittal, axial, and coronal grids were 0.69 [0.57], 0.61 [0.49], and 0.78 [0.44], respectively). Kendall's tau values showed strong agreement (average 0.73) between distributions, which were statistically significant (p < 0.05) apart from a single coronal grid in one model and two sagittal grids of another. Conclusions: CFD modeling demonstrates statistical agreement with in vitro experimental results. This validation study is one of the largest of its kind and supports the applicability of CFD in accurately modeling nasal spray drug delivery and using computational methods to investigate means of improving clinical drug delivery.
