Issue link: https://www.e-digitaleditions.com/i/1518209
Inhalation April 2024 11 ery from the impactor characterizes the fraction of the dose that might realistically be expected to pene- trate through the nasal cavity to the lung. Using this test set-up helps analysts and product developers investigate and understand important issues such as: • How successful is delivery to the olfactory region across different formulations or with different excipients? • Which of these devices is preferable for delivery to the turbinates? • How does the inclusion of a mucoadhesive in the formulation affect deposition behavior? • Can the deposition profile of this nasal powder be improved via particle engineering? • What proportion of the delivered dose is likely to penetrate to the lungs with this formulation/ device combination? nasal cavity: the vestibule, valve, anterior turbinate, posterior turbinate, olfactory and nasopharynx. Using seven realistic adult nasal geometries derived from CT scans of adults averaging 60 years old (male and female), simulations were carried out to investi- gate the effect of particle diameter, spray cone angle, spray release direction, particle injection speed and particle injection location [6]. e results were then validated against in vivo deposi- tion data (where available) and with respect to exper- imentally measured vs. calculated pressure drop [8]. An idealized nasal geometry capable of adequately reflecting averaged behavior was then determined via numerical methods and simulation to mimic the aver- aged deposition behavior observed across the in silico data sets [7]. e resulting geometry was physically realized via stereolithography, enabling the manufac- ture of the first, plastic AINI with four regions (ves- tibule, turbinates, olfactory and nasopharynx). is device was shown to successfully mimic in vivo depo- sition behavior [3, 8] and an AINI with the same geometry was subsequently designed and manufac- tured in aluminum to extend suitability for a wider range of nasal drug products (Figure 1). Figure 2 shows a test set-up for nasal sprays incor- porating the AINI. e automated shake and fire system is used to eliminate the variability introduced by manual actuation in line with the US Pharma- copoeia (USP) recommendation to use "a mechani- cal means of actuating the metering system or pump assembly to deliver doses for collection" when testing nasal sprays and aerosols [9]. A nosepiece adapter is sometimes used to allow experimentation with inser- tion depth and a greater range of devices. e AINI is easily opened, post drug delivery, to enable recovery from each of the four regions (Figure 1). Drug recov- Figure 1 The Alberta Idealised Nasal Inlet (AINI), shown in closed position (left) and dismantled for drug recovery (right). Nasopharynx Olfactory Vestibule Turbinates Figure 2 Instruments for nasal spray testing; incorporating the AINI with the Next Generation Impactor (NGI) and an automated actuation platform.