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28 June 2024 Inhalation tion performance), indicating that the combination of dissolution and biorelevant drug release testing can represent a robust screening methodology for ASD for nasal delivery. Conclusion Nasal powders have been recognized as an opportu- nity to improve stability and residence time on the nasal mucosa compared with liquids, where amor- phous powders favor the formulation of poorly sol- uble drugs with improved biopharmaceutical profile, namely faster onset of action. However, regulatory recommendations and consensus in the scientific community on how to evaluate nasal powder per- formance are limited. Moreover, the industry and academia face gaps among particle engineering, formulation and product in vitro and in vivo per- formance. erefore, this article presents two case studies focused on particle engineering strategies and nasal powder formulation of a model poorly soluble drug for systemic delivery, while evaluating perfor- mance methodologies. e results confirm the suitability of spray drying to manufacture particles for nasal delivery. is pro- cess is scalable and can be fine-tuned to meet particle size requirements. Spray-dried microparticles of the model poorly soluble drug exhibited higher deposi- tion on the turbinates area than chimeral agglomer- ates and blend formulations, evidencing spray drying as a suitable technology for nasal targeted systemic delivery. e findings also showed that amorphous solid dispersions generate supersaturated solutions, resulting in enhanced in vitro release performance using a biorelevant methodology. Pharmacokinetic studies conducted in Wistar rats confirmed the potential of ASD to provide faster onset of action for poorly soluble drugs, given the shorter t max of the model amorphous formulations. is indicates that supersaturation, even when maintained for a short period of time, affects and promotes absorption. In vitro nasal deposition and drug release methodol- ogies proved to be helpful in selecting lead formu- lations. Formulation screening and in vitro/in vivo correlations are valuable in early phase formulation development, reducing in vitro and in vivo testing in later stage formulation development. e product complexity and limited regulatory guid- ance in nasal powder development demands collab- oration and input from multiple areas in order to expedite progress in this field. Despite the challenges, the studies performed can foster better comprehen- sion of formulation, process and performance evalu- ation of nasal powders. dissolution profiles of the blends, only the blend with HPMC was selected for the in vivo studies, in order to minimize the number of animals used. Plasma samples were collected for 30 hours after adminis- tration. e main pharmacokinetic parameters of the concentration-time profile are summarized in Table 1, as estimated by non-compartmental analy- sis. SDM of HPMC presented the highest C max and shortest t max , suggesting a faster absorption of PXC. For this formulation, PXC plasma concentration at 20 minutes was significantly higher (p < 0.01) than the other formulations. is indicates that SDM of HPMC could provide a faster onset of action with quicker and effective therapeutic action. e amor- phous SDM formulations provided lower t max than the blend containing crystalline drug, indicating that the faster drug release provided by these formulations has, as expected, impact on drug absorption. SDM of PVP/VA provided the second highest C max , followed by the blend with HPMC. is indicates that ASD for nasal delivery of poorly soluble drugs could be a suitable strategy to provide a faster onset of action and especially useful in therapeutic indications such as pain management, migraine or angina pectoris [1]. e formulation rankings obtained in dissolution and drug release studies at early timepoints (up to 1 hour) were predictive regarding in vivo t max (shorter for for- mulations with higher dissolution performance) and C max (higher for formulations with higher dissolu- Pharmacokinetic Parameters SDM PVP/VA a SDM HPMC a Blend HPMC a t max (h) 2.33 0.89 3.33 C max (µg/mL) 3.35 4.68 3.26 AUC 1h (µg.h/mL) 2.16 3.63 1.78 AUC 30h (µg.h/mL) 46.05 41.06 44.70 a Parameters estimated considering a normalized PXC dose of 0.3 mg AUC 1h : area under the concentration time- curve from time zero to 1 hour AUC 30h : area under the concentration time- curve from time zero to 30 hours CA: chimeral agglomerates C max : maximum peak concentration HPMC: hydroxypropyl methylcellulose PVP/VA: polyvinylpyrrolidone/vinyl acetate SDM: spray-dried microparticles t max : time to achieve the maximum peak concentration Table 1 Pharmacokinetic parameters following intranasal or intravenous administration of piroxicam, evaluated by non-compartmental analysis.