Robinson Keila, Mock Charlotta, Liang Dong
a Department of Pharmaceutical Sciences , Texas Southern University , Houston , TX , USA.
Drug Dev Ind Pharm. 2015;41(9):1464-9. doi: 10.3109/03639045.2014.958753. Epub 2015 Jul 21.
Resveratrol, a natural compound found in grapes, has potential chemotherapy effects but very low oral bioavailability in humans.
To evaluate the solubility, pH stability profile, plasma protein binding (PPB) and stability in plasma for resveratrol.
Solubility of resveratrol was measured in 10 common solvents at 25 °C using HPLC. The solution state pH stability of resveratrol was assessed in various United States Pharmacopeia buffers ranging from pH 2 to 10 for 24 h at 37 °C. Samples were analyzed up to 24 h. Human PPB was determined using ultracentrifugation technique. Standard solutions of drug were spiked to blank human plasma to yield final concentrations of 5, 12.5 or 25 μg/mL for determination. Finally, stability of resveratrol in human and rat plasma was also assessed at 37 °C. Aliquots of blank plasma were spiked with a standard drug concentration to yield final plasma concentration of 50 μg/mL. Samples were analyzed for resveratrol concentration up to 96 h.
Resveratrol has wide solubility ranging from 0.05 mg/mL in water to 374 mg/mL in polyethylene glycol 400 (PEG-400). Resveratrol is relatively stable above pH 6 and has maximum degradation at pH 9. The mean PPB of resveratrol is 98.3%. Resveratrol degrades in human and rat plasma in a first-order process with mean half lives of 54 and 25 h, respectively.
Resveratrol is more soluble in alcohol and PEG-400 and stable in acidic pH. It binds highly to plasma proteins and degrades slower in human then rat plasma.
白藜芦醇是一种存在于葡萄中的天然化合物，具有潜在的化疗作用，但在人体中的口服生物利用度非常低。
评估白藜芦醇的溶解度、pH稳定性、血浆蛋白结合率（PPB）及在血浆中的稳定性。
采用高效液相色谱法（HPLC）在25℃下测定白藜芦醇在10种常用溶剂中的溶解度。在37℃下，于pH值2至10的各种美国药典缓冲液中评估白藜芦醇的溶液状态pH稳定性，持续24小时。对样品进行长达24小时的分析。采用超速离心技术测定人血浆蛋白结合率。将药物标准溶液加入空白人血浆中，使其最终浓度分别为5、12.5或25μg/mL进行测定。最后，还在37℃下评估白藜芦醇在人和大鼠血浆中的稳定性。将空白血浆等分试样加入标准药物浓度，使其最终血浆浓度为50μg/mL。对样品进行长达96小时的白藜芦醇浓度分析。
白藜芦醇具有广泛的溶解度，在水中为0.05mg/mL，在聚乙二醇400（PEG - 400）中为374mg/mL。白藜芦醇在pH值6以上相对稳定，在pH值9时降解最大。白藜芦醇的平均血浆蛋白结合率为98.3%。白藜芦醇在人和大鼠血浆中以一级过程降解，平均半衰期分别为54小时和25小时。
白藜芦醇在乙醇和PEG - 400中更易溶解，在酸性pH条件下稳定。它与血浆蛋白高度结合，在人血浆中的降解速度比大鼠血浆慢。
