DOI
https://doi.org/10.25772/72VA-RG15
Defense Date
2017
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Pharmaceutical Sciences
First Advisor
Dr. Michael Hindle
Second Advisor
Dr. Peter Byron
Third Advisor
Dr. Jurgen Venitz
Fourth Advisor
Dr. P. Worth Longest
Fifth Advisor
Dr. Amy Pakyz
Abstract
The overall objectives of this research project were i) to develop and evaluate methods of characterizing nasal spray products using realistic nasal airway models as more clinically relevant in vitro tools and ii) to develop and evaluate a novel high-efficiency antibiotic nanoparticle dry powder formulation and delivery device. Two physically realistic nasal airway models were used to assess the effects of patient-use experimental conditions, nasal airway geometry and formulation / device properties on the delivery efficiency of nasal spray products. There was a large variability in drug delivery to the middle passages ranging from 17 – 57 % and 47 – 77 % with respect to patient use conditions for the two nasal airway geometries. The patient use variables of nasal spray position, head angle and nasal inhalation timing with respect to spray actuation were found to be significant in determining nasal valve penetration and middle passage deposition of Nasonex®. The developed test methods were able to reproducibly generate similar nasal deposition profiles for nasal spray products with similar plume and droplet characteristics. Differences in spray plume geometry (smaller plume diameter resulted in higher middle passage drug delivery) were observed to have more influence on regional nasal drug deposition than changes to droplet size for mometasone furoate formulations in the realistic airway models.
Ciprofloxacin nanoparticles with a mean (SD) volume diameter of 120 (10) nm suitable for penetration through mucus and biofilm layers were prepared using sonocrystallization technique. These ciprofloxacin nanoparticles were then spray dried in a PVP K30 matrix to form nanocomposite particles with a mean (SD) volume diameter of 5.6 (0.1) µm. High efficiency targeted delivery of the nanocomposite nasal powder formulation was achieved using a modified low flow VCU DPI in combination with a novel breathing maneuver; delivering 73 % of the delivered dose to the middle passages. A modified version of the nasal airway model accommodating Transwell® inserts and a Calu-3 monolayer was developed to allow realistic deposition and evaluation of the nasal powder. The nanocomposite formulation was observed to demonstrate improved dissolution and transepithelial transport (flux = 725 ng/h/cm2) compared to unprocessed ciprofloxacin powder (flux = 321 ng/h/cm2).
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
5-10-2017