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12 April 2024 Inhalation is last question can also be assessed via established methods for nasal testing in line with the United States Food and Drug Administration (FDA) requirements to determine the drug mass associ- ated with fine particles by cascade impaction, to demonstrate BE [10]. Typically, a 2-L glass expan- sion chamber is used to interface the nasal spray and impactor but by advantageously providing an accu- rate representation of deposition in the nasal cavity and, by extension, a reliably representative sample for the impactor, the AINI offers potential for more clinically realistic assessment. e other questions are only answerable by using some form of nasal cast or representative nasal inlet. ere is a growing body of work with the AINI described in the open literature. For example, Henriques et al. used the AINI to benchmark alternative particle engineering strategies for nasal powders [11] and in an extension study to assess the potential of amorphous solid dispersions [12]. In addition, Murphy et al. applied the AINI to assess the delivery characteristics of a novel, spray- dried tuberculosis vaccine [13]. In the following sections, and as stated above, we now summarize three studies that demonstrate the application of the AINI to address three key aspects of nasal drug product testing and development. Study 1. Comparing in vitro and in vivo performance for different types of nasal drug product In a study by Chen et al., the AINI was used to investigate the deposition behavior of a range of liq- uid nasal drug products for the treatment of nasal allergy symptoms: an aqueous solution formula- tion (NasalCrom; Johnson & Johnson, New Bruns- wick, NJ, US); an aqueous suspension formulation (Nasonex; MSO, Rahway, NJ, US) and a nasal pres- surized metered dose inhaler or aerosol (QNASL; Tevam Tel Aviv-Yafo, Israel) [14]. Tests were carried out by mechanically actuating each product into the metal AINI and analyzing the amount of drug that a) dripped onto a cotton wipe held below the inlet, b) deposited in each section of the inlet and c) was captured on a filter, post inlet. A flow rate of 7.5 L/min was selected to simulate breathing through a single nostril and spray orientation angle was varied (45 o and 60 o ) in line with routinely reported values from the literature. Results were reported as a frac- tion of the total amount deposited in the AINI with deposits from the turbinates and olfactory region grouped as "mid- and upper nasal" to facilitate com- parison with available in vivo gamma scintigraphy data [15, 16]. e measured data indicate that generally, the AINI successfully mimics deposition behavior for all three product types (Figure 3) with no statistically signif- Figure 3 Comparison of regional deposition in vivo (red) with AINI data measured at a spray orientation angle of 45° (light grey) and 60° (dark grey) for NasalCrom (left), Nasonex (center) and QNASL (right). Reproduced with permission from Respiratory Drug Delivery 2022, RDD Online. 1.1 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 Fraction of Deposited Dose Nose (Ve) Mid + Upper Nasal (Tu + OI) 1.1 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 Fraction of Deposited Dose Nose (Ve) Mid + Upper Nasal Throat (Na) (Tu + OI) 1.1 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 Fraction of Deposited Dose Nose (Ve) Mid + Upper Nasal Throat (Na) (Tu + OI)