BACKGROUND: Curcumin has a wide spectrum of biological and pharmacological activities, but it has not yet been approved as a therapeutic agent because of its low solubility and stability in aqueous solution, and the relatively low bioavailability in vivo. To overcome these limitations, self-microemulsifying drug delivery system (SMEDDS) of curcumin was developed. METHOD: Various oils, surfactants, and cosurfactants were selected to optimize the formulation. Pseudoternary phase diagrams were constructed and orthogonal design was used to compare the oil-in-water (o/w) microemulsion-forming capacity of different oils/surfactants/cosurfactants. The solubility of curcumin in various oils and cosurfactants was determined to find suitable ingredients with a good solubilizing capacity. Droplet size was measured to obtain the concentration of oil, surfactant, and cosurfactant for forming stable microemulsion. Furthermore, its quality and bioavailability in mice were assessed. RESULTS: Pseudoternary phase diagrams and solubility test showed that the formulation of SMEDDS composed of 20% ethanol, 60% Cremophor RH40®, and 20% isopropyl myristate, in which the concentration of curcumin reached 50 mg/mL. Curcumin was released completely from SMEDDS at 10 minutes. The developed SMEDDS formulation improved the oral bioavailability of curcumin significantly, and the relative oral bioavailability of SMEDDS compared with curcumin suspension was 1213%. CONCLUSION: The SMEDDS can significantly increase curcumin dissolution in vitro and bioavailability in vivo.
BACKGROUND:Curcumin has a wide spectrum of biological and pharmacological activities, but it has not yet been approved as a therapeutic agent because of its low solubility and stability in aqueous solution, and the relatively low bioavailability in vivo. To overcome these limitations, self-microemulsifying drug delivery system (SMEDDS) of curcumin was developed. METHOD: Various oils, surfactants, and cosurfactants were selected to optimize the formulation. Pseudoternary phase diagrams were constructed and orthogonal design was used to compare the oil-in-water (o/w) microemulsion-forming capacity of different oils/surfactants/cosurfactants. The solubility of curcumin in various oils and cosurfactants was determined to find suitable ingredients with a good solubilizing capacity. Droplet size was measured to obtain the concentration of oil, surfactant, and cosurfactant for forming stable microemulsion. Furthermore, its quality and bioavailability in mice were assessed. RESULTS: Pseudoternary phase diagrams and solubility test showed that the formulation of SMEDDS composed of 20% ethanol, 60% Cremophor RH40®, and 20% isopropyl myristate, in which the concentration of curcumin reached 50 mg/mL. Curcumin was released completely from SMEDDS at 10 minutes. The developed SMEDDS formulation improved the oral bioavailability of curcumin significantly, and the relative oral bioavailability of SMEDDS compared with curcumin suspension was 1213%. CONCLUSION: The SMEDDS can significantly increase curcumin dissolution in vitro and bioavailability in vivo.
Authors: María L Del Prado-Audelo; Isaac H Caballero-Florán; Jorge A Meza-Toledo; Néstor Mendoza-Muñoz; Maykel González-Torres; Benjamín Florán; Hernán Cortés; Gerardo Leyva-Gómez Journal: Biomolecules Date: 2019-02-08