10th International Aerosol Conference September 2 - September 7, 2018 America's Center Convention Complex St. Louis, Missouri, USA
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Patient Specific Deposition Enhancement of Nasal Sprays in Ct-Derived Human Nasal Replicas
Landon Holbrook, ALYSSA BURKE, Saikat Basu, Elizabeth Monaghan, Julia Kimbell, William Bennett, University of North Carolina at Chapel Hill
Abstract Number: 1651 Working Group: Aerosols in Medicine
Abstract A patient specific nozzle positioning device (NPD) was developed to enhance delivery of a nasal spray in an individualized nasal model of a patient post functional endoscopic sinus surgery (FESS). Preliminary computational fluid dynamics (CFD) simulations were used to determine administration angles for improved delivery to the maxillary sinus. Penetration depth past the nasal valve was established as a metric to assess improvement compared to standard of care (SOC) use as specified by package insert instructions.
Methods: De-identified sinus CT scans were used to digitally reconstruct the nasal cavity of a patient before and after FESS. Hollow models of the nasal cavity including external nares were 3D-printed in flexible and rigid parts to allow for nostril distension due to the insertion of a nasal spray bottle. The angle of administration was fixed1) according to SOC instructions or 2) for the NPD based on CFD simulation on the post-FESS model results. The NPD was retrofitted for testing on the pre-FESS model without CFD simulations. The SOC use condition was tilting the head at 22.5 degrees forward with an upright bottle inserted to a depth of one centimeter. Steady inspiratory airflow at a flow rate derived from subject weight was drawn through the model during administration of a nasal spray (one spray in left nostril) spiked with the radioactive tracer Tc99m. Radio-aerosol deposition was assessed using a 2D gamma camera. Images of the models in the coronal plane were used to quantify sinus deposition, while images in the sagittal plane were used for penetration measures. Four replicate experiments were conducted to determine the mean and standard deviation (SD) of deposition. Coefficient of variation (CoV) is used to estimate consistency between experiments and is determined by dividing the SD of the deposition by the calculated mean.
Results: Preliminary results for a single subject showed that the mean (SD) fraction of sprayed drug depositing posterior to the nasal valve was 8.0 (2.7) % of the total dose in the pre-FESS model and 11.4 (2.3) % of the total dose in the post-FESS model using SOC administration. Administration of the nasal spray with the NPD produced a mean (SD) fraction of posterior deposition of 12.7 (5.2) % in the pre-FESS model and 15.8 (1.4) % in the post-FESS model. The CoV was 20.4% using the SOC administration and 8.8% using the NPD in the post-FESS model. However, the CoV was 34.2% using the SOC administration and 41.1% using the NPD in the pre-FESS model.
Conclusions: SOC administration of a nasal spray product was measured using gamma scintigraphy and increased 42% when comparing a pre-FESS surgery model to a post-FESS model. Use of the NPD provided a 39.0% increase in deposition posterior to the nasal valve in the post-FESS model. Variability was reduced for the post-FESS model, likely because the NPD was a better fit for this model. Additional subject models are being tested to determine if the NPD will consistently reduce the variability in administered dose. While the novel positioning device coupled with surgery improved delivery of a nasal spray past the nasal valve from 8.0% to 15.8%., there is a remaining 84.2% of the drug depositing prior to the nasal valve that is not expected to provide any therapeutic effect. Supported by NIH HL122154.