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Interest in intranasal drug delivery serves as a stimulus to improve in vitro test methods towards greater relevance and utility [1, 2]. A tool for in vitro studies of regional deposition in the nasal cavity is highly desirable within this context and in 2020, Chen, et al. released studies showing the potential of an idealized nasal inlet for this purpose [3]. 10 April 2024 Inhalation Exploring application of an idealized nasal inlet Interest in intranasal drug delivery serves as a stimu- lus to improve in vitro test methods towards greater relevance and utility [1, 2]. A tool for in vitro stud- ies of regional deposition in the nasal cavity is highly desirable within this context and in 2020, Chen, et al. released studies showing the potential of an idealized nasal inlet for this purpose [3]. is inlet, which has since been developed by the same pioneering group that introduced the Alberta Idealised roat (AIT) geometries to support the more clinically relevant testing of orally inhaled products (OIPs) [4-6], has become known as the Alberta Idealised Nasal Inlet (AINI). e AINI has been designed from computer tomography (CT) scans of realistic adult geometries and extensive computational fluid dynamic (CFD) simulations, and early experimental studies have shown that it mimics the averaged deposition behav- ior of complex models of the nasal cavity [3]. e AINI serves several valuable purposes. Firstly, it enables the in vitro assessment of regional deposition within the nose, for products in development. is assessment is a critical concern as researchers refine their understanding as to where and how to target nasal drug delivery for optimal therapeutic effect, for different classes of drug. Secondly, the AINI is beneficial for generic developers seeking to replicate the performance of a reference product. For solu- tion-based, topical nasal sprays, strictly comparable deposition in the nasal cavity provides valuable sup- porting evidence of bioequivalence (BE). irdly, by relevantly reflecting the dose captured in the nasal cavity, the AINI provides a more clinically represen- tative assessment of the dose that might penetrate to the lung, relative to compendial nasal drug prod- uct testing apparatuses. Pulmonary deposition is an important safety issue associated with intranasal drug delivery since drugs approved for topical relief are not necessarily approved, or safe, for systemic absorption. In this article, we describe the development and vali- dation of the AINI, illustrating its use within existing test set-ups and examining the information gener- ated. We then discuss three experimental studies that demonstrate: 1) the ability of the AINI to capture in vivo deposi- tion behavior for different nasal drug products 2) use of the AINI to assess and optimize formula- tions for intranasal vaccination and 3) how the AINI enables more realistic assessment of the risk of pulmonary deposition Development and validation of the AINI for in vitro studies Using nasal casts to study regional deposition is com- mon practice, facilitated in recent years by ease of manufacture via processes such as stereolithography and other forms of 3D printing. Such casts have been shown to generate data that correlate closely with in vivo results and are helpful in accelerating prog- ress towards focused in vivo testing [3, 7]. However, they are often developed from just a single subject. Given the inter-subject variability observed in nasal geometry, even within a specific patient population (e.g., adult, child), this is an important limitation that complicates the robust assessment of deposition behavior, and indeed, inter-laboratory comparison. e concept of an "averaged" or idealized nasal inlet addresses this issue. Investigators pursued this goal of an "averaged" yet realistic nasal inlet, first with extensive computa- tional fluid dynamic (CFD) studies [3, 8, 9]. ese studies were carried out across a wide parameter space to investigate deposition in six regions of the Improving the utility of in vitro test methods for intranasal drug delivery Enhancing the clinical relevance of in vitro testing techniques Clair Brooks, PhD and Matthew Fenn, MBA Copley Scientific