Abstract
In this study, amorphous solid dispersions (ASDs) of pterostilbene (PTR) with polyvinylpyrrolidone polymers (PVP K30 and VA64) were prepared through milling, affirming the amorphous dispersion of PTR via X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). Subsequent analysis of DSC thermograms, augmented using mathematical equations such as the Gordon-Taylor and Couchman-Karasz equations, facilitated the determination of predicted values for glass transition (T(g)), PTR's miscibility with PVP, and the strength of PTR's interaction with the polymers. Fourier-transform infrared (FTIR) analysis validated interactions maintaining PTR's amorphous state and identified involved functional groups, namely, the 4'-OH and/or -CH groups of PTR and the C=O group of PVP. The study culminated in evaluating the impact of amorphization on water solubility, the release profile in pH 6.8, and in vitro permeability (PAMPA-GIT and BBB methods). In addition, it was determined how improving water solubility affects the increase in antioxidant (ABTS, DPPH, CUPRAC, and FRAP assays) and neuroprotective (inhibition of cholinesterases: AChE and BChE) properties. The apparent solubility of the pure PTR was ~4.0 µg·mL(-1) and showed no activity in the considered assays. For obtained ASDs (PTR-PVP30/PTR-PVPVA64, respectively) improvements in apparent solubility (410.8 and 383.2 µg·mL(-1)), release profile, permeability, antioxidant properties (ABTS: IC(50) = 52.37/52.99 μg·mL(-1), DPPH: IC(50) = 163.43/173.96 μg·mL(-1), CUPRAC: IC(0.5) = 122.27/129.59 μg·mL(-1), FRAP: IC(0.5) = 95.69/98.57 μg·mL(-1)), and neuroprotective effects (AChE: 39.1%/36.2%, BChE: 76.9%/73.2%) were confirmed.