DOI

10.17077/etd.igyp-db7u

Document Type

Dissertation

Date of Degree

Fall 2018

Access Restrictions

Access restricted until 01/31/2021

Degree Name

PhD (Doctor of Philosophy)

Degree In

Pharmaceutical Sciences and Experimental Therapeutics

First Advisor

Donovan, Maureen D.

First Committee Member

Donovan, Maureen D.

Second Committee Member

Stevens, Lewis L.

Third Committee Member

Govindarajan, Ramprakash

Fourth Committee Member

Milavetz, Gary

Fifth Committee Member

Peters, Thomas M.

Abstract

Nasal sprays used for the treatment of cold and allergy symptoms use same device and formulation in children and adults. Owing to the obvious differences in nasal cavity dimensions between adults and children, the performance of nasal sprays products in children needs to be critically assessed.

In an effort to evaluate the deposition patterns of nasal sprays administered to children, a nasal cast based on MRI images obtained from a 12-year-old child’s nasal cavity was developed using 3D printing technology. Glycerin-water mixtures providing sprays with a range of plume angles (26° - 62°), along with three additional commercial nasal sprays, were investigated by actuating the device into the cast under controlled conditions. Following spray administration, the cast was disassembled and subjected to image analysis followed by quantification of formulation deposition in each section of the cast using both chemical and image analysis. The results showed that nasal sprays impacted entirely in the anterior region of the 12-year-old child’s nasal cavity and limited amount of spray entered the turbinate region – the effect site for most topical drugs.

Additional experiments were conducted to measure the deposition patterns of nasal sprays in the presence of a mucus layer on the surface of the nasal cast. In an effort to make the nasal deposition studies more relevant to human nasal conditions, the mucus coated nasal cast was tilted in order to induce a physical movement of the mucus layer from the anterior region to the nasopharynx. The presence of mucus did not result in a significant increase in the turbinate region deposition but tilting of the mucus coated nasal cast resulted in 20% - 40% deposition in the turbinate region, improving the posterior region deposition of sprays. Even with the enhanced posterior movement nearly 60% of the spray formulations remained in the anterior region, a site with poor absorption characteristics.

The computational fluid dynamic simulations evaluated the impact of multiple parameters including plume angle, droplet diameter and administration conditions on the deposition of nasal sprays in the 12-year-old child’s nasal cavity. The simulations showed significant anterior deposition for all plume angles (10° – 50°) and droplet diameters (30 µm – 400 µm) tested, similar to the observations from the in vitro experiments. An additional parameter, the direction of nasal spray actuation in the nasal cavity, was identified as a critical factor improving the turbinate region deposition of sprays in the 12-year-old child’s nasal cavity in spite of the narrow nasal valve region.

Keywords

Anterior deposition, Nasal spray, Pediatrics, Plume angle

Pages

xx, 175 pages

Bibliography

Includes bibliographical references (pages 167-175).

Copyright

Copyright © 2018 Namita Ajay Sawant

Available for download on Sunday, January 31, 2021

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