Development of a Resveratrol Nanosuspension Using the Antisolvent Precipitation Method without Solvent Removal, Based on a Quality by Design (QbD) Approach

Abstract

The purpose of this study was to develop a resveratrol nanosuspension with enhanced oral bioavailability, based on an understanding of the formulation and process parameters of nanosuspensions and using a quality by design (QbD) approach. Particularly, the antisolvent method, which requires no solvent removal and no heating, is newly applied to prepare resveratrol nanosuspension. To ensure the quality of the resveratrol nanosuspensions, a quality target product profile (QTPP) was defined. The particle size (z-average, d90), zeta potential, and drug content parameters affecting the QTPP were selected as critical quality attributes (CQAs). The optimum composition obtained using a 3-factor, 3-level Box–Behnken design was as follows: polyvinylpyrrolidone vinyl acetate (10 mg/mL), polyvinylpyrrolidone K12 (5 mg/mL), sodium lauryl sulfate (1 mg/mL), and diethylene glycol monoethyl ether (DEGEE, 5% v/v) at a resveratrol concentration of 5 mg/mL. The initial particle size (z-average) was 46.3 nm and the zeta potential was −38.02 mV. The robustness of the antisolvent process using the optimized composition conditions was ensured by a full factorial design. The dissolution rate of the optimized resveratrol nanosuspension was significantly greater than that of the resveratrol raw material. An in vivo pharmacokinetic study in rats showed that the area under the plasma concentration versus time curve (AUC0–12h) and the maximum plasma concentration (Cmax) respectively, than those of the resveratrol raw material. Therefore, the prepara values of the resveratrol nanosuspension were approximately 1.6- and 5.7-fold higher,tion of a resveratrol nanosuspension using the QbD approach may be an effective strategy for the development of a new dosage form of resveratrol, with enhanced oral bioavailability.

Resveratrol Suppresses Cross-Talk between Colorectal Cancer Cells and Stromal Cells in Multicellular Tumor Microenvironment: A Bridge between In Vitro and In Vivo Tumor Microenvironment Study

“…However, it should be noted that the low bioavailability and rapid metabolism of resveratrol in the body not only limits its therapeutic and biological effects, but also causes some changes in the way resveratrol is administered. In fact, numerous studies have been conducted to improve the bioavailability of resveratrol, and an important method of administering resveratrol is nano-based systems [ 87 ]. Interestingly, it has been reported that lipid nano-capsules loaded with resveratrol have higher anti-oxidant and anti-inflammatory effects than resveratrol alone [ 88 ].…”

Pure Trans-Resveratrol Nanoparticles Prepared by a Supercritical Antisolvent Process Using Alcohol and Dichloromethane Mixtures: Effect of Particle Size on Dissolution and Bioavailability in Rats

“…The blood samples were centrifuged (12,000 rpm, 5 min), and plasma was collected and stored at −70 • C until HPLC analysis. The concentration of trans-resveratrol in plasma was determined using a previously reported method and under HPLC analysis conditions [16,41]. The AUC 0→8h was calculated using the linear trapezoidal method.…”

“…Further, its benefits are affected after its oral administration owing to its poor solubility and instability in physiological conditions as well as extensive metabolism [8,9]. To date, several formulation strategies such as amorphous solid dispersions, composite nanoparticles, emulsions, liposomes, polymeric micelles, self-emulsifying drug delivery systems, and solid lipid nanoparticles have been investigated to resolve this problem [10][11][12][13][14][15][16][17][18][19]. In addition, the enhanced oral bioavailability in humans has been reported with lipid formulation, micellar liquid formulation, and microparticles mixed with a liquid formulation [20][21][22].…”

Natural products and phytochemical nanoformulations targeting mitochondria in oncotherapy: an updated review on resveratrol

“…So, it is obvious that poor bioavailability of resveratrol not only has limited its therapeutic and biological impacts, but also has led to some effects on the administration route of resveratrol. A variety of attempts have been performed to improve the bioavailability of resveratrol and among them, the nano-based drug delivery systems are of importance [35]. In a newly published article, Thipe and colleagues synthesized resveratrol-loaded gold nanoparticles to enhance the anti-tumor potential of resveratrol against breast, pancreatic and prostate cancers.…”