Characterizing regional drug delivery within the nasal airways

ABSTRACT

Introduction

The nose has been receiving increased attention as a route for drug delivery. As the site of deposition constitutes the first point of contact of the body with the drug, characterization of the regional deposition of intranasally delivered droplets or particles is paramount to formulation and device design of new products.

Areas covered

This review article summarizes the recent literature on intranasal regional drug deposition evaluated in vivo, in vitro and in silico, with the aim of correlating parameters measured in vitro with formulation and device performance. We also highlight the relevance of regional deposition to two emerging applications: nose-to-brain drug delivery and intranasal vaccines.

Expert opinion

As in vivo studies of deposition can be costly and time-consuming, researchers have often turned to predictive in vitro and in silico models. Variability in deposition is high due in part to individual differences in nasal geometry, and a complete predictive model of deposition based on spray characteristics remains elusive. Carefully selected or idealized geometries capturing population average deposition can be useful surrogates to in vivo measurements. Continued development of in vitro and in silico models may pave the way for development of less variable and more effective intranasal drug products.

KEYWORDS:

• Nasal drug delivery
• intranasal vaccines
• spray drying
• nose-to-brain delivery
• olfactory
• turbinates
• nasal sprays
• powders

Article highlights

• Emerging therapeutic modalities like nose-to-brain delivery and intranasal vaccination highlight the importance of regional deposition of droplets or particles in the nose for drug developers.

• Various imaging methods can assess regional deposition in vivo, but are frequently slow, labor intensive, and suffer from a number of other drawbacks. On the other hand, correlations of benchtop in vitro tests of nasal drug products currently recommended by regulators with in vivo regional deposition have not been established.

• Validated in vitro and in silico assessments using nasal casts or geometries can strike a balance between clinical relevance and research effort while improving mechanistic understanding of delivery.

• Droplet or particle size is not the only predictor of regional deposition in the nasal cavity; in vitro and in vivo studies have shown that device orientation also plays a decisive role.

• Considerable variability in regional deposition exists due to variability in the morphology of individual nasal cavities. Hence, consistent and precise targeting of specific regions of the nasal cavity remains elusive.

• Due to intersubject variability, it is unlikely that a randomly chosen nasal geometry will be representative of a population. Thus, for in vitro or in silico testing, standardization around one representative geometry or set of geometries would facilitate more direct comparisons of regional deposition data.

Declaration of interest

A Martin and W Finlay are co-inventors of the AINI geometry, which is licensed by the University of Alberta to Copley Scientific through a royalty-bearing agreement. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.