Amorphous nasal powder advanced performance: in vitro/ex vivo studies and correlation with in vivo pharmacokinetics

Abstract Purpose Amorphous solid dispersions (ASD) for nasal delivery offer the opportunity to increase drug release performance, while using polymers with mucoadhesive properties. The aim of present study was apply this solubility enhancement technique a poorly soluble delivery, comparing two particle engineering strategies, namely spray dried microparticles and chimeral agglomerates, corresponding physical blends crystalline drug. Methods Formulations piroxicam were manufactured varied polymer strategies evaluated through in vitro ex vivo permeation studies, as well deposition pharmacokinetic studies. Results ASD hydroxypropyl methylcellulose (HPMC) showed enhanced permeation, compared polyvinylpyrrolidone/vinyl acetate formulations blends. Nasal HPMC agglomerates suggested off-target deposition. In studies revealed that spray-dried HPMC-containing exhibited highest maximum plasma concentration (C max ) lowest time attain it (t ). rate absorption correlated t performance. When excluding formulation least targeted deposition, performance also C area under concentration-time curve (AUC) from 0 1 h, R 2 > 0.89. Conclusion provide fast absorption, which depends on supersaturation ability employed. vitro-in correlations are predictive tools regarding absorption.