Formulation of Stable, Free-Flowing, Fast-Disintegrating Granules of Volatile Essential Oils for Olfactory Rehabilitation

This study designs stable fast-disintegrating oral granules (FDGs) of volatile liquid essential oils (cinnamon, lemon, rose, and peppermint oils) for olfactory rehabilitation. By adsorbing liquid-type essential oils onto colloidal silicon dioxide (1:1 w/w) and incorporating olive oil (1:1:0.25 w/w) as a volatile restrainer, the retention of major odorants—cinnamaldehyde, citral, phenethyl alcohol, and menthol—in cinnamon, lemon, rose, and peppermint oils, respectively, was markedly improved after 12 h of exposure at 40 °C. Then, free-flowing FDG system was formulated with sugar alcohols (mannitol, xylitol, and sorbitol), low substituted hydroxypropyl cellulose, and magnesium stearate, exhibiting rapid spreading and disintegration (<31.2 s) upon contact with aqueous media. The package of FDGs into four-layer laminated pouch afforded markedly prevent volatility of olfactory components, preserving >82% of cinnamaldehyde, citral, phenethyl alcohol, and menthol for 8 weeks under 25 °C/65% relative humidity (RH) conditions. In an in vitro volatilization test, major odorants were effectively volatilized from artificial saliva-wetted FDGs within 90 min depending on the volatility of each constituent. Therefore, this novel oral FDG system is expected to be a promising alternative for olfactory training for neurogenic smell dysfunction, providing enhanced storage stability, precise dosing, and patient compliance.