Sustained-Release Solid Dispersion of High-Melting-Point and Insoluble Resveratrol Prepared through Hot Melt Extrusion to Improve Its Solubility and Bioavailability

Abstract

This study aimed to prepare a sustained-release solid dispersion of poorly water-soluble resveratrol (RES) with high melting point in a single hot melt extrusion step. A hydrophobic–hydrophilic polymeric blend (Eudragit RS and PEG6000) was used to control the release of RES. With the dispersive mixing and high shear forces of hot melt extrusion, the thermodynamic properties and dispersion of RES were changed to improve its solubility. The effects of the formulation were investigated through univariate analysis to optimize the preparation of the sustained-release solid dispersion. In vitro and in vivo studies were performed to evaluate the prepared RES/RS/PEG6000 sustained-release solid dispersion. The physical state of the solid dispersion was characterized using differential scanning calorimetry and X-ray diffraction. Surface properties of the dispersion were visualized using scanning electron microscopy, and the chemical interaction between RES and excipients was detected through Fourier-transform infrared spectroscopy. Results suggested that the optimized sustained-release solid dispersion was obtained when the mass ratio of RES-polymeric blend was 1:5, the ratio of PEG6000 was 35%, the barrel temperature was 170 °C, and the screw speed was 80 rpm. In vitro studies demonstrated that the solid dispersion showed a good sustained release effect. The cumulative release of RES reached 82.42% until 12 h and was fit by the Weibull model. In addition, the saturated solubility was 2.28 times higher than that of the bulk RES. In vitro studies demonstrated that the half-life increased from 3.78 to 7.09 h, and the bioavailability improved to 140.38%. The crystalline RES was transformed into the amorphous one, and RES was highly dispersed in the polymeric blend matrix.

A comparative study on the preparation and evaluation of solubilizing systems for silymarin

“…As depicted in Fig. 4A, the FTIR spectra of SM, PVPK30, and F68 exhibited a resemblance to the previously reported patterns [50,51]. The and 996 cm − 1 (O-H out plane bending, benzopyran ring) [50,52].…”

Solid Dispersions of Genistein via Solvent Rotary Evaporation for Improving Solubility, Bioavailability, and Amelioration Effect in HFD-Induced Obesity Mice

“…The solubility of GEN in SDs with pH 6.8 phosphate buffer was measured using a shake-flask method. An excess amount of GEN was added to the above solutions, which were transferred to an air bath thermostatic shaker at 37 °C for 24 h. The solution was filtered through a 0.22 µm membrane filter [ 26 ]. The GEN concentration was measured at λ max 261 nm using a UV spectrophotometer 6850 (Jenway, Chicago, IL, USA).…”

Traditional Chinese medicine monomers: Targeting pulmonary artery smooth muscle cells proliferation to treat pulmonary hypertension

“…The effective concentration of it in serum is only trace levels [ 33 ]. Therefore, a lot of teams are committed to developing new dosage forms, such as melt extrusion method for the high melting point of insoluble resveratrol slow-release solid dispersions, resveratrol with two magnesium hydroxide as the carrier (Resv @ MDH), resveratrol phospholipid complex self-microemulsion drug delivery system, etc., which significantly improve the solubility and bioavailability of resveratrol [ [34] , [35] , [36] ]. Additionally, Li et al [ 37 ] confirmed that dipalmitoylphosphatidylcholine-coated lipid nanoparticles (DPPC-LNs) as inhalable carriers could accumulate resveratrol in pulmonary vessels, which inhibited 5-hydroxytryptamine (5-HT)-induced proliferation of PASMCs, and 25–200 μM Res-DPPC-LNs had no effect on their viability.…”