Development of self-microemulsifying lipid-based formulations of trans-resveratrol by systematically constructing lipid-surfactant-water phase diagrams using long-chain lipids

Abstract

The aim of this work was to develop self-microemulsifying lipid-based formulations of trans-resveratrol in cod liver oil, a long chain lipid, to increase its solubility, dissolution rate and oral bioavailability. Ternary phase diagrams of cod liver oil with surfactant and water as well as pseudo-ternary phase diagrams of the same by mixing cod liver oil (triglyceride) with glycerol monooleate (monoglyeride) were constructed to identify regions where microemulsions were formed. Kolliphor RH 40, Tween 80 and their 1:1-mixtures were evaluated as surfactants. No organic cosolvents were added. It was observed that cod liver oil alone did not form microemulsion with any of the surfactants used, and a 1:1 mixture of cod liver oil and glycerol monooleate was necessary to enable the formation of microemulsion. Among the surfactants, Kolliphor RH 40 provided the maximum microemulsification effect. Several formulations containing 6:4, 1:1, and 4:6 w/w ratios of lipid to surfactant using the 1:1 mixture of cod liver oil and glycerol monooleate as lipid components and Kolliphor RH 40 or its mixture with Tween 80 as surfactants were identified, and trans-resveratrol solubility in these formulations were determined. Drug concentrations used in the formulations were 80% of saturation solubility, and no organic cosolvents were used in any formulations to increase drug solubility or enable emulsification. In vitro dispersion testing in 250 mL of 0.01 N HCl (pH 2) according to the USP method 2 at 50 RPM showed that the formulations rapidly dispersed in aqueous media forming microemulsions and there was no drug precipitation.

Keywords:

• Lipid-based formulations
• microemulsion
• SMEDDS
• trans-resveratrol
• cod liver oil
• long chain lipid
• glycerol monoglyceride
• surfactant
• phase diagram
• solubility

Acknowledgements

The experimental part of this study was conducted in the summer of 2018 when Dr. Carolina Aloisio was a Fullbright Scholar at St. John’s University in the USA. The financial support from Fondo para la Investigación Científica y Tecnológica” (FONCYT) PICT 2015 Code 0790, Consejo Nacional de Investigaciones Científicas y Técnicas” (CONICET) and Secretaría de Ciencia y Técnica de la Universidad Nacional de Córdoba (SECyT-UNC) is greatly appreciated. Authors also wish to acknowledge the assistance from the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), the Universidad Nacional de Córdoba and the Fulbright Commission.

Disclosure statement

The authors report no conflict of interest.