Optimization of a Self-microemulsifying Drug Delivery System for Oral Administration of the Lipophilic Drug, Resveratrol: Enhanced Intestinal Permeability in Rat

• Published in: Advanced pharmaceutical bulletin Vol. 13; no. 3; pp. 521 - 531
• Main Authors: Mirzaeei, Shahla, Tahmasebi, Negar, Islambulchilar, Ziba
• Format: Journal Article
• Language: English
• Published: Tabriz Tabriz University of Medical Sciences 01.07.2023
• Subjects: antioxidant; Antioxidants; Bioavailability; Design of experiments; Drug delivery systems; Drugs; intestinal permeability; Microemulsions; Oral administration; oral drug delivery; Permeability; Polyethylene glycol; resveratrol; self-micro emulsifying drug delivery systems; single-pass intestinal perfusion; Software; Surfactants; Vegetable oils; Germany
• ISSN: 2228-5881; 2251-7308
• DOI: 10.34172/apb.2023.054

Purpose: This study aimed to formulate Resveratrol, a practically water-insoluble antioxidant in a self-microemulsifying drug delivery system (SMEDDS) to improve the solubility, release rate, and intestinal permeability of the drug. Methods: The suitable oil, surfactant, and co-surfactant were chosen according to the drug solubility study. Utilizing the design of experiment (DoE) method, the pseudo-ternary phase diagram was plotted based on the droplet size. In vitro dissolution study and the single-pass intestinal perfusion were performed for the investigation of in vitro and in-situ permeability for drugs formulated as SMEDDS in rat intestine using High-Performance Liquid Chromatography. Results: Castor oil, Cremophor RH60, and PEG 1500 were selected as oil, surfactant, and co-surfactant. According to the pseudo-ternary phase diagram, nine formulations developed microemulsions with sizes ranging between 145-967 nm. Formulations passed the centrifuge and freeze-thaw stability tests. The optimum formulation possessed an almost 2.5-fold higher cumulative percentage of in vitro released resveratrol, in comparison to resveratrol aqueous suspension within 120 minutes. The results of the in-situ permeability study suggested a 2.6-fold higher intestinal permeability for optimum formulation than that of the resveratrol suspension. Conclusions: SMEDDS can be considered suitable for the oral delivery of resveratrol according to the observed increased intestinal permeability, which could consequently enhance the bioavailability and therapeutic efficacy of the drug.