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Inhalation June 2024 25 within the nasal size range (Dv50 of 10 to 45 µm) [39] and primary particles for agglomeration (Dv50 of 2 to 3 µm). Chimeral agglomerates were pro- duced by vibrating primary particles in a sieve shaker equipped with 106 µm and 710 µm mesh size sieves, and collecting the agglomerates retained on top of the 106 µm sieve. Physical blends were obtained by mixing neat polymer microparticles with piroxicam raw material in a Turbula ® blender (WAB-Group. Muttenz, Switzerland). All formulations were pro- duced at 20% (w/w) drug load. Nasal deposition was evaluated using the AINI coated with Brij solution and coupled with a Next Generation Impactor (NGI, Copley Scientific). A 45° administration angle and 15 L/min inhalation flow were the experimental conditions selected for the nasal deposition studies. e nasal deposition results show that the particle engineering strategy affects the nasal deposition pro- file (Figure 2). e average deposition on the vesti- bule and turbinates was higher for SDM, followed by blends and CA, with statistically significant differences between SDM and CA on the turbinates (p < 0.05, two-way ANOVA) except between SDM, HPMC and CA HPMC (p = 0.077), demonstrating SDM to be an advantageous particle engineering strategy for nasal targeted systemic delivery. HPMC-based CA showed high deposition on the NGI stages (24.0 ± 9.5%), with 12.9% deposition on NGI stage 1 (d50 > 14.1 µm) and 3.7% deposition on NGI stages 5 and 6 (1.36 < d50 < 3.3 µm). is last fraction of the for- mulation can deposit on small airways and the alveoli region since particles are within the aerodynamic size range of 1 to 5 µm. is suggests the agglomerates may break into fragments that can reach the lungs (Figure 2). CA required an extra manufacturing step and presented a higher risk of lung deposition since the size of primary particles was in the inhalation size range. Overall, SDM within the nasal size range was the most promising particle engineering strategy to target nasal systemic absorption. Supersaturating ASD for fast onset of action through the nasal mucosa A large number of lipophilic compounds with poor solubility have been emerging in the drug discov- ery pipeline. In fact, more than three-quarters of new drugs in development are poorly soluble [5], a characteristic that negatively affects drug dissolution and, subsequently, systemic absorption. erefore, many technologies have been developed to enhance drug solubility such as amorphous solid dispersion (ASD), where a drug is homogenously dispersed in an excipient matrix in an amorphous state. An amor- phous form of drug occurs in a higher free- energy state compared to its crystalline counterpart, pro- viding enhanced solubility and dissolution rate [40]. Additionally, amorphous solids can promote super- Benchmarking of particle engineering strategies for nasal powder delivery Polymeric nasal powders can be manufactured by different particle engineering strategies including blending of drug and excipient(s), spray drying or agglomeration of primary particles into chimeral agglomerates (CA) [35]. While spray drying allows particle size control and generation of amorphous solid dispersions, blending is simpler and CA may allow faster dissolution after breakup into smaller particles. e objective of this study was to charac- terize nasal deposition and benchmark nasal powders manufactured by different particle engineering strat- egies, namely spray-dried microparticles (SDM), CA and blends, using the Alberta Idealised Nasal Inlet (AINI, Copley Scientific, Nottingham, UK). e AINI (Figure 1) is an idealized nasal airway geometry constructed of aluminum, developed according to computational fluid dynamics simula- tions performed in a set of realistic nasal geometries, in order to mimic human nasal deposition [36, 37]. It has four different regions, namely the vestibule (nostril), the turbinates, the olfactory region and the nasopharynx, which can be separated, allowing drug quantification. e AINI can be coupled with a Next Generation Impactor (NGI), providing additional information about lung deposition [38]. In total, six different formulations of a model drug were prepared using two polymers and three parti- cle engineering strategies. e non- steroidal anti- inflammatory drug (NSAID) piroxicam was selected as a model poorly soluble drug with analgesic charac- teristics, due to its potential for rapid pain relief when administered through nasal delivery, compared to the conventional oral route. Polyvinylpyrrolidone/vinyl acetate (PVP/VA) and hydroxypropyl methylcellu- lose E3 (HPMC) were selected as polymers. Spray drying was performed using an ultrasonic (USN) and two-fluid nozzle (TFN) to produce microparticles Figure 1 Alberta Idealised Nasal Inlet (AINI) coupled with the Next Generation Impactor (NGI). Reproduced with permission from Copley Scientific, Limited [38].