Controlled release of oral tetrahydrocurcumin from a novel self-emulsifying floating drug delivery system (SEFDDS)

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.

Fig. 1

Chemical structures of curcumin (a) and tetrahydrocurcumin (b)

Fig. 2

Pseudo-ternary phase diagrams composed of various oils and surfactants. The surfactant phase was as follows: Cremophor RH40 (a), Cremophor EL (b), Cremophor RH40/PEG 400 (1:1) (c), Cremophor EL/PEG 400 (1:1) (d), Cremophor EL/Labrasol (1:1) (e, f). The oil phase was as follows: Capryol 90 (a–e) and Labrafac PG/Capryol 90 (1:1) (f). The gray area represents the range of existence of a microemulsion, the white area represents the coarse emulsion ranges, and the gray–black area represents the gel-like phases. Broken line represents the aqueous dilution line A20 from the non-aqueous vehicle to the water axis (on this dilution line, the weight ratio of surfactant/oil phase is constant at 7:3)

Fig. 3

TEM micrographs of THC-SEDDS (S6) (×100,000). Bar = 50 nm

Fig. 4

Representative image of a THC-SEFDDS pellet of F2 formulation

Fig. 5

Representative SEM micrographs of the surfaces and cross-sections of the THC self-emulsifying floating pellet formulation (F2). a (×60) and b (×500) surface of pellets before THC release; c (×60) and d (×500) surface of pellets after THC release; e (×150) cross-section of pellets before THC release; f (×150) cross-section of pellets after THC release

Fig. 6

Floating ability of THC-SEFDDS pellet formulations with different proportions of glyceryl behenate. Values represent a mean±SD of three replicates. Note: formulation F2 has the same composition as formulation F6 (Fig. 7)

Fig. 7

Floating ability of THC-SEFDDS pellet formulations with different proportions of sodium starch glycolate. Values represent a mean±SD of three replicates. Note: formulation F6 has the same composition as formulation F2 (Fig. 6)

Fig. 8

Release profiles of THC from THC-SEFDDS with different proportions of glyceryl behenate in simulated gastric fluid (SGF, pH 1.2) without pepsin. Data represents the mean±SD (n = 3). Note: formulation F2 has the same composition as formulation F6 (Fig. 9)

Fig. 9

Release profiles of THC from THC-SEFDDS with different proportions of sodium starch glycolate in simulated gastric fluid (SGF, pH 1.2) without pepsin. Data represents the mean±SD (n = 3). Note: formulation F6 has the same composition as formulation F2 (Fig. 8)

Fig. 10

Release profiles of THC from THC-SEFDDS (F2) compared with release from THC-SEDDS and dissolution of unformulated THC in simulated gastric fluid (SGF, pH 1.2) without pepsin. Data represents the mean±SD (n = 3)