Spray-freeze-drying aprepitant with hydroxypropyl cellulose increases nasal bioavailability.

The design of free-flowing lyophilized powders by spray-freeze-drying (SFD) enables novel therapeutic applications, including nasal administration. In this study, a non-aqueous SFD approach using dimethyl sulfoxide (DMSO) as the spray solvent was investigated. Low-viscosity hydroxypropyl cellulose grades (HPC-SSL and HPC-UL) were employed as excipients to produce rapidly dissolving, porous, amorphous aprepitant powders at different drug-to-polymer ratios. The resulting spherical particles contained amorphous aprepitant and exhibited sizes between 250 μm and 500 μm. In vitro dissolution at pH 7.0 showed rapid drug release, with maximum dissolution achieved after 3 min for aprepitant/HPC-UL at a 20/80 ratio, exceeding the corresponding physical mixture by 2- to 3-fold. Film-cast amorphous solid dispersions (ASDs) reached comparable drug concentrations but exhibited slower dissolution. Formulations containing HPC-SSL showed higher supersaturation levels but reduced dissolution rates. Increasing drug loading to a 40/60 ratio led to a marked delay in dissolution. Nasal deposition in vitro exceeded 90% of the administered dose, attributed to the combination of low particle density (<0.1 g/cm3) and sufficient mechanical stability. Following nasal administration in rats, t max ranged from 0.8 h to 4 h, C max from 26.9 ng/ml to 64.0 ng/ml, and AUClast from 125.4 ng·h/ml to 316.3 ng·h/ml, with no statistically significant differences between HPC-UL and HPC-SSL. All SFD formulations demonstrated significantly increased nasal bioavailability compared to ASD controls. Despite similar t max values, HPC-based SFD formulations enhanced aprepitant bioavailability by at least threefold. These findings underline the potential of SFD as a formulation platform for the nasal delivery of poorly water-soluble drugs.