Mixed lipid phase SMEDDS as an innovative approach to enhance resveratrol solubility

Abstract

Context: Despite its promising therapeutic activities, clinical use of resveratrol (RSV) is compromised with unfavorable biopharmaceutical properties, namely low water solubility.Objective: This work deals with improving RSV solubility and release rate through its incorporation in innovative mixed lipid phase self-microemulsifying drug delivery systems (SMEDDS).Methods: (Pseudo)ternary diagrams were constructed for different oils and surfactant mixtures. Selected systems were further evaluated for RSV solubility, self-emulsification ability, accelerated stability, dynamic viscosity, compatibility with hard gelatin capsules and in vitro dissolution of RSV.Results: Lipid phase composed of diverse lipid species, castor oil (long-chained triglyceride) and Capmul MCM (mixture of medium chain mono and diglycerides) allowed formulation of mixed lipid SMEDDS with lower surfactants content (60% Cremophor EL/RH 40/RH 60). Mixed lipid phase SMEDDS showed best self-emulsifying ability with regard to self-emulsifying time as well as droplet size and monodispersity of microemulsions obtained upon SMEDDS dilution with aqueous phase. Overall, incorporation of RSV in SMEDDS resulted in improved solubility (over 23-fold) and dissolution rate compared to crystalline RSV. All SMEDDS formulations were adequately viscous for filling into hard gelatin capsules (>150 mPaċs for empty SMEDDS; >400 mPaċs for RSV-loaded SMEDDS) and no leaking was observed during three months of storage.Conclusion: The presented work indicates the promising potential of mixed lipid SMEDDS formulations for future development of SMEDDS with lower surfactant content and no added cosolvents for incorporation of RSV and other poorly soluble drugs.