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Inhalation June 2024 27 ree formulations, namely HPMC SDM, PVP/VA SDM and HPMC blend formulations, were charac- terized for pharmacokinetic profile after nasal admin- istration to Wistar rats. Considering the similar Franz diffusion cells (PermeGear, Inc., Hellertown, PA, US) were then applied to study the drug release profile of the PXC powder formulations. Contrary to the dissolution experiment, this methodology allows mimicking physiological conditions of the nasal cav- ity, including temperature, medium and slow powder hydration in a humid environment similar to that encountered in the nasal cavity [48]. e percentage of PXC released was plotted as a function of time (Figure 3B). e PVP/VA-based SDM showed higher percentages of drug release than the corresponding blend for the first 3 hours, while for the HPMC-based SDM this was valid for the 8 hours of the test. Addi- tionally, from the 20-minute timepoint onward, the SDM of HPMC exhibited significantly (p < 0.001, ANOVA) higher percentage of drug release, when compared to all other formulations. Blend formula- tions presented a slower release, with major differ- ences seen in the first 2 hours, most likely due to the crystalline state of the drug. A supersaturated solu- tion generated by the amorphous form of the drug can increase the amount of drug available to cross the artificial membrane, where the polymer plays a major role in the ability to achieve and maintain supersat- uration [7]. As observed in dissolution experiments, HPMC sustains the supersaturated drug for a longer period of time, allowing a higher drug release. Even though PVP/VA may promote some degree of super- saturation, the faster drug precipitation hinders the release rate. e small volume used in the MicroDiss Profiler dissolution experiments proved to be helpful in characterizing the "spring and parachute" behavior of ASD [49] and ranking the formulations correctly. Figure 3 Dissolution profile (A) and in vitro drug release profile (B) of piroxicam powder formulations. Results are expressed as mean ± standard deviation (n = 3). HPMC: hydroxypropyl methylcellulose; PVP/VA: polyvinylpyrrolidone/vinyl acetate; SDM: spray-dried microparticles. Concentration (µg/mL) 150 100 50 0 A Time (hr) 0 1 2 3 4 5 6 SDM PVP/VA SDM HPMC Blend PCP/VA Blend HPMC Drug Released 15 10 5 0 B Time (hr) 0 1 2 3 4 5 6 SDM PVP/VA SDM HPMC Blend PCP/VA Blend HPMC