Pre-formulation studies of resveratrol

Context: Resveratrol, a natural compound found in grapes, has potential chemotherapy effects but very low oral bioavailability in humans. Objective: To evaluate the solubility, pH stability profile, plasma protein binding (PPB) and stability in plasma for resveratrol. Methods: Solubility of resveratrol was measured in 10 common solvents at 25 degrees 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 degrees 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 ng/mL for determination. Finally, stability of resveratrol in human and rat plasma was also assessed at 37 degrees C. Aliquots of blank plasma were spiked with a standard drug concentration to yield final plasma concentration of 50 ng/mL. Samples were analyzed for resveratrol concentration up to 96h. Results: 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. Conclusion: 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.