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Abstract. The objectives of this study were to develop and evaluate a novel self-emulsifying floating drug delivery system (SEFDDS) that resulted in improved solubility, dissolution, and controlled release of the poorly water-soluble tetrahydrocurcumin (THC). The formulations of liquid self-emulsifying drug delivery system (SEDDS; mixtures of Labrasol, Cremophor EL, Capryol 90, Labrafac PG) were optimized by solubility assay and pseudo-ternary phase diagram analysis. The liquid SEDDS was mixed with adsorbent (silicon dioxide), glyceryl behenate, pregelatinized starch, sodium starch glycolate, and microcrystalline cellulose and transformed into pellets by the extrusion/spheronization technique. The resulting pellets with 22% liquid SEDDS had a uniform size and good self-emulsification property. The microemulsions in aqueous media of different self-emulsifying floating pellet formulations were in a particle size range of 25.9-32.5 nm. Use of different weight proportions of glyceryl behenate and sodium starch glycolate in pellet formulations had different effects on the floating abilities and in vitro drug release. The optimum formulation (F2) had a floating efficiency of 93% at 6 h and provided a controlled release of THC over an 8-h period. The release rate and extent of release of THC liquid SEDDS (80% within 2 h) and self-emulsifying floating pellet formulation (80% within 8 h) were significantly higher than that of unformulated THC (only 30% within 8 h). The pellet formulation was stable under intermediate and accelerated storage conditions for up to 6 months. Controlled release from this novel SEFDDS can be a useful alternative for the strategic development of oral solid lipid-based formulations.

Tetrahydrocurcumin (THC), one of the curcumin metabolites, exhibits pharmacological activities such as antioxidant, anti-inflammatory and anti-carcinogenic properties. However, the pharmacological effect of THC is limited due to its low aqueous solubility. Floating alginate beads containing self-emulsifying drug delivery system (SEDDS) of THC were developed to increase drug solubility and prolong gastric residence time. Use of different weight proportions of sodium alginate (Na-alg.), calcium chloride (CaCl2) and water soluble pore former (Polyvinylalcohol-polyethylene glycol copolymer; Kollicoat® IR) in bead formulations had different effects on the floating abilities and in vitro rate of THC release. The release profile of the optimized THC-SEDDS floating alginate beads (D3) indicated a significant increase in the dissolution rate of THC and provided a controlled release of THC over an 8 h period in a simulated gastric fluid. The release of about 80% of THC from the optimized beads as an o/w microemulsion with a particle size of less than 50 nm, compared to only 30 % by an aqueous suspension from the unformulated THC could be considerable greater absorbed. The self-emulsifying floating alginate beads may provide a useful solid dosage form for oral delivery of THC and other hydrophobic compounds.

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