The Development and Optimisation of a Spinosin Solid-Dispersion-Based Functional Dairy Beverage and Its...

Insomnia remains a widespread global health issue, and traditional hypnotic drugs often produce adverse effects. Although spinosin in Ziziphi Spinosae Semen has sleep-promoting effects, its use is limited by poor solubility and low oral bioavailability. In this study, the solvent melt method was used to prepare spinosin solid dispersions, optimising the process with an L₉(3⁴) orthogonal design based on apparent solubility. In vitro dissolution testing showed that solid dispersions of varying particle sizes dissolved more readily than pure spinosin, with smaller particles exhibiting faster dissolution. Cellular uptake was assessed in human colon adenocarcinoma cells, with results revealing enhanced uptake of smaller-particle solid dispersions. Powder X-ray diffraction confirmed that spinosin transformed from a crystalline to an amorphous state in the dispersion system. A quadratic orthogonal experiment was conducted to optimise functional dairy beverage formulation, using the centrifugal sedimentation rate as the evaluation index. In vivo experiments demonstrated that the resulting functional dairy beverage reduced spontaneous activity in mice, achieved a 60% sleep-onset rate, improved ethanol-induced memory impairment and produced marked sleep-promoting effects. Moreover, pharmacokinetic studies confirmed that the spinosin solid-dispersion-based functional dairy beverage significantly enhanced the systemic exposure and oral bioavailability of spinosin compared to the spinosin water suspension. These findings indicate that solid dispersion technology effectively enhances spinosin solubility and that the developed functional dairy beverage shows promise as a sleep-promoting functional food.