Curcumin phytosomal softgel formulation: Development, optimization and physicochemical characterization

Abstract

Curcumin, a naturally occurring lipophilic molecule can exert multiple and diverse bioactivities. However, its limited aqueous solubility and extensive presystemic metabolism restrict its bioavailability. Curcumin phytosomes were prepared by a simple solvent evaporation method where free fl owing powder was obtained in addition to a newly developed semisolid formulation to increase curcumin content in soft gels. Phytosomal powder was characterized in terms of drug content and zeta potential. Thirteen diff erent soft gel formulations were developed using oils such as Miglyol 812, castor oil and oleic acid, a hydrophilic vehicle such as PEG 400 and bioactive surfactants such as Cremophor EL and KLS P 124. Selected formulations were characterized in terms of curcumin in vitro dissolution. TEM analysis revealed good stability and a spherical, self-closed structure of curcumin phytosomes in complex formulations. Stability studies of chosen formulations prepared using the hydrophilic vehicle revealed a stable curcumin dissolution patt ern. In contrast, a dramatic decrease in curcumin dissolution was observed in case of phytosomes formulated in oily vehicles.Keywords: curcumin, phospholipid, phytosomes, bioavailability, lipids, soft gels INTRODUCTION Curcumin (CUR) found in the turmeric rhizomes can exert multiple and diverse bioactivities, including antioxidant, antitumor, anti-inflammatory, antidiabetic, antirheumatic, wound healing, antiviral, hepatoprotective, and anti-HIV activity (1). Despite the potential biological eff ects of CUR, poor bioavailability in both rodents and humans, as reported in several pharmacokinetic studies (2), demands high doses to reach therapeutic drug levels. Detectable serum levels were not achieved until doses of up to 3.6 g were used; consequently, a 3.6 g daily dose of oral CUR was used in the phase II clinical trial in patients with advanced colorectal cancer (3). Keeping in mind the promise of CUR as a therapeutically active agent and its poor oral absorption due to its limited aqueous solubility and extensive presystemic metabolism, it is necessary to develop a new formulation of CUR that could augment its oral absorption and enhance its therapeutic activity.To improve the bioavailability of CUR, numerous approaches and technologies have been investigated over the past decades, including the use of solid dispersion (4), copolymeric micelles (5), polymeric nanoparticles (6), lipid based nanoparticles (7), self microemulsion (8), liposomes (9) and complexation with phospholipids (10, 11). All these approaches are expected to provide bioavailability enhancement and improved absorption in the intestinal tract.Phytosomes are considered to be a safe and convenient delivery system, able to enhance oral bioavailability of poorly water soluble drugs. Their safety is related to the similarity between their structural components and the lipid content of mammalian cell membranes (12)(13)(14). Phytosomes show a bett er stability profi le than liposomes due to the unique chemical bond interact...

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