In vitro evaluation of regional nasal drug delivery using multiple anatomical nasal replicas of adult human subjects and two nasal sprays

Michele Dario Manniello; Sana Hosseini; Ali Alfaifi; Amir R Esmaeili; Arun V Kolanjiyil; Ross Walenga; Andrew Babiskin; Dennis Sandell; Reza Mohammadi; Theodore Schuman; Michael Hindle; Laleh Golshahi

doi:10.1016/j.ijpharm.2020.120103

In vitro evaluation of regional nasal drug delivery using multiple anatomical nasal replicas of adult human subjects and two nasal sprays

Int J Pharm. 2021 Jan 25:593:120103. doi: 10.1016/j.ijpharm.2020.120103. Epub 2020 Nov 23.

Affiliations

¹ Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, VA, USA.
² Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, VA, USA; Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, USA.
³ Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
⁴ S5Consulting, Blentarp, Sweden.
⁵ Department of Otolaryngology- Head and Neck Surgery, VCU Health, Richmond, VA, USA.
⁶ Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, USA.
⁷ Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, VA, USA. Electronic address: lgolshahi@vcu.edu.

PMID: 33242586
DOI: 10.1016/j.ijpharm.2020.120103

Abstract

Quantifying drug delivery to the site of action using locally-acting nasal suspension sprays is a challenging but important step toward understanding bioequivalence (BE) between test and reference products. The main objective of this study was to investigate the in vitro deposition pattern of two common but different locally-acting nasal suspension sprays using multiple nasal cavities. Twenty anatomically accurate nasal replicas were developed from high-resolution sinonasal computed tomography scans of adults with healthy nasal airways. The airways were segmented into two regions of anterior and posterior to the internal nasal valve. Both sides of the septum were considered separately; hence, 40 nasal cavities were studied. The positioning of the spray nozzle in all 40 cavities was characterized by the head angle, coronal angle, and the insertion depth. Despite using a controlled protocol to minimize the anterior losses, a wide range of variability in posterior drug delivery was observed. The observed intersubject variability using this in vitro method may have important implications for understanding BE of locally-acting nasal suspension sprays.

Keywords: Anatomical variability; Drug deposition; In vitro bioequivalence; Nasal replica; Nasal spray.

MeSH terms

Administration, Intranasal
Adult
Aerosols
Humans
Nasal Cavity / diagnostic imaging
Nasal Sprays*
Nose*
Research Subjects

Substances

Aerosols
Nasal Sprays