Third-Generation Solid Dispersion Through Lyophilization Enhanced Oral Bioavailability of Resveratrol

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Biopharmaceutics

Background:

• Resveratrol (RES) exhibits low solubility and bioavailability, limiting its therapeutic efficacy.
• Solid dispersions (SDs) are a promising strategy to enhance the oral bioavailability of poorly soluble drugs like RES.

Purpose of the Study:

• To develop a third-generation RES solid dispersion (SD) using lyophilization to improve solubility, dissolution, and oral bioavailability.
• To characterize the solid-state properties and amorphous conversion of RES within the SD.

Main Methods:

• Formulation of RES third-generation SD using Eudragit E PO (hydrophilic carrier) and Gelucire 44/14 (surfactant) via lyophilization.
• Solid-state characterization using DSC, SEM, FTIR, PLM, XRPD, and particle size analysis.
• In vitro solubility, dissolution, and intestinal permeability studies (Caco-2 models).
• In vivo oral bioavailability assessment in Wistar rats.

Main Results:

• The third-generation SD demonstrated significantly increased RES solubility (8-12 fold) and dissolution rates (5-fold at pH 6.8) compared to pure RES and physical mixtures.
• Enhanced in vitro intestinal permeability was observed in Caco-2 models (2.4-fold increase).
• In vivo studies showed a 3-fold increase in RES oral bioavailability compared to a second-generation SD.

Conclusions:

• Lyophilized third-generation RES SD effectively improves solubility, dissolution, and oral bioavailability.
• The enhanced bioavailability is attributed to improved solubility, dissolution, and potentially reduced RES metabolism and P-gp efflux.
• This formulation strategy offers a viable approach to maximize the therapeutic potential of resveratrol.