Rosiak Natalia, Tykarska Ewa, Cielecka-Piontek Judyta
Department of Pharmacognosy and Biomaterials, Faculty of Pharmacy, Poznan University of Medical Sciences, 3 Rokietnicka St., 60-806 Poznan, Poland.
Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, 3 Rokietnicka St., 60-806 Poznan, Poland.
Int J Mol Sci. 2024 Feb 28;25(5):2774. doi: 10.3390/ijms25052774.
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), 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 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), release profile, permeability, antioxidant properties (ABTS: IC = 52.37/52.99 μg·mL, DPPH: IC = 163.43/173.96 μg·mL, CUPRAC: IC = 122.27/129.59 μg·mL, FRAP: IC = 95.69/98.57 μg·mL), and neuroprotective effects (AChE: 39.1%/36.2%, BChE: 76.9%/73.2%) were confirmed.
在本研究中，通过研磨制备了芪三酚（PTR）与聚乙烯吡咯烷酮聚合物（PVP K30和VA64）的无定形固体分散体（ASD），并通过X射线粉末衍射（XRPD）和差示扫描量热法（DSC）确定了PTR的无定形分散状态。随后，利用Gordon-Taylor和Couchman-Karasz方程等数学方程对DSC热谱图进行分析，有助于确定玻璃化转变温度（T）的预测值、PTR与PVP的混溶性以及PTR与聚合物相互作用的强度。傅里叶变换红外光谱（FTIR）分析验证了维持PTR无定形状态的相互作用，并确定了相关的官能团，即PTR的4'-OH和/或-CH基团以及PVP的C=O基团。该研究最终评估了非晶化对水溶性、pH 6.8条件下的释放曲线以及体外渗透性（PAMPA-GIT和BBB方法）的影响。此外，还确定了提高水溶性如何影响抗氧化性能（ABTS、DPPH、CUPRAC和FRAP测定）和神经保护性能（胆碱酯酶抑制：AChE和BChE）的增强。纯PTR的表观溶解度约为4.0 μg·mL，在所考虑的测定中未显示活性。对于获得的ASD（分别为PTR-PVP30/PTR-PVPVA64），表观溶解度（分别为410.8和383.2 μg·mL）、释放曲线、渗透性、抗氧化性能（ABTS：IC = 52.37/52.99 μg·mL，DPPH：IC = 163.43/173.96 μg·mL，CUPRAC：IC = 122.27/129.59 μg·mL，FRAP：IC = 95.69/98.57 μg·mL）和神经保护作用（AChE：39.1%/36.2%，BChE：76.9%/73.2%）均得到了证实。
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