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26 June 2024 Inhalation dissolution and drug release profile, using simulated nasal fluid [47]. Subsequently, in vivo pharmacoki- netic studies were carried out in Wistar rats for select formulations. e SDM of PXC presented no crys- talline peaks on X-ray powder diffraction diffracto- grams, confirming the formation of an ASD. Small volume dissolution testing in a MicroDiss Pro- filer (Pion, Inc., Billerica, MA, US) was carried out to investigate the supersaturation potential of the formu- lations varying in manufacturing strategy and poly- meric composition. e results (Figure 3A) show that the amorphous formulations comprising PVP/VA or HPMC generate a supersaturated solution when in contact with the medium. A PXC concentration of approximately 130 µg/mL was attained for both SDM formulations at 5 minutes, which was about 7 times higher than the concentration attained with the blends. However, this supersaturated state was transient with recrystallization of metastable super- saturated PXC. For PVP/VA SDM, this occurred quickly, with an abrupt reduction of dissolved PXC after 5 minutes, leading to low PXC concentrations that were similar to blends after 4 hours. For HPMC SDM, the decrease was slower and concentrations were maintained higher than those dissolved from blends for the 6 hours of the test. is indicates that HPMC has higher capacity to maintain the supersat- urated state of PXC in solution. saturation of the drug during dissolution [41]. e supersaturated solution in the nasal mucosa may enhance drug permeation and bioavailability, partic- ularly when absorption is limited by drug solubility [20, 42, 43]. An ASD can be manufactured by spray drying, a scalable process that allows particle size control. Poly- mers commonly used in ASD, such as HPMC and PVP/VA [7], have mucoadhesive properties [44-46] and, therefore, a dual function: stabilizing the drug amorphous form and enhancing mucoadhesion, which increases both dissolution and residence time of the formulation. However, the impact of differ- ent polymers on drug release performance, in many instances, is still not clear and the methodologies available to evaluate the behavior of these formu- lations are limited. Guidelines from European and US regulators lack recommendations on advanced nasal powder performance characterization, namely regarding drug release, mucoadhesion and perme- ation. Accordingly, the objective of this study was to characterize the in vitro and in vivo performance of amorphous spray-dried microparticles (SDM) comprising a model poorly soluble drug piroxicam (PXC) and either HPMC or PVP/VA, at 20% drug load, while comparing with the corresponding phys- ical blends [47]. To achieve this, the SDM and blend formulations manufactured as described in the pre- vious study were evaluated regarding their in vitro Figure 2 Nasal deposition profile of powder formulations using the AINI coupled with the NGI. CA: chimeral agglomerates; HPMC: hydroxypropyl methylcellulose; PVP/VA: polyvinylpyrrolidone/vinyl acetate; SDM: spray-dried microparticles. *p < 0.05 and ***p < 0.001 were considered statistically significant. Fraction of Dose (% w/w) 60 50 40 30 20 10 0 NGI Stages Capsule Nasopharynx Turbinates Olfactory Vestibule SDM PVP/VA SDM HPMC CA PVP/VA CA HPMC Blend PCP/VA Blend HPMC