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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 the present study was to apply this solubility enhancement technique to a poorly soluble drug for nasal delivery, while comparing two particle engineering strategies, namely spray dried microparticles and chimeral agglomerates, with the corresponding physical blends with crystalline drug.

Methods
Formulations of piroxicam were manufactured using varied polymer and particle engineering strategies and evaluated through "in vitro" drug release and "ex vivo" permeation studies, as well as nasal deposition and "in vivo" pharmacokinetic studies.

Results
ASD with hydroxypropyl methylcellulose (HPMC) showed enhanced drug release and permeation, compared to polyvinylpyrrolidone/vinyl acetate formulations and blends. Nasal deposition of HPMC chimeral agglomerates suggested off-target deposition. "In vivo" pharmacokinetic studies revealed that spray-dried HPMC-containing microparticles exhibited the highest maximum plasma concentration (Cmax) and the lowest time to attain it (tmax). "In vitro" release rate and "in vivo" absorption rate were correlated as well as tmax and "in vitro" performance. When excluding the formulation with least nasal targeted deposition, "in vitro" release and "ex vivo" permeation performance were also correlated with Cmax and area under the drug concentration-time curve (AUC) from 0 to 1 h, with R2 > 0.89.

Conclusion
ASD for nasal delivery provide fast drug absorption, which depends on the supersaturation ability of the polymer employed. "In vitro-in vivo" correlations suggested that "in vitro" release and "ex vivo" permeation studies are predictive tools regarding nasal absorption.

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