Novel poorly water-soluble curcumin-loaded modified drug delivery systems with enhanced solubility and oral bioavailability

Abstract

Chapter 1: Two types of solid dispersions, solvent-evaporated and surface-attached, were formulated using a spray-drying technique and their ability to improve the aqueous solubility and oral bioavailability of poorly water-soluble curcumin was evaluated. Among the solid dispersions fabricated, those which presented the highest oral bioavailability were selected. Among the carriers investigated, Kollidon VA64 and sodium lauryl sulfate (SLS) which substantially enhance drug solubility, were selected as the applicable polymer and surfactant, respectively. Various curcumin-loaded solid dispersion formulations were prepared, and their solubility and dissolution were examined to compare with those of curcumin powder. The composition of curcumin, Kollidon VA64, and SLS using ethanol in a weight ratio of 1:10:0.3 and using distilled water in a weight ratio of 1:0.7:0.3 were chosen as the potential formulations of solvent-evaporated and surface-attached solid dispersions, respectively, considering that they demonstrated the most increased drug solubility and dissolution. The former produced a spherical and amorphous state of the drug with a reduced particle size. However, in the latter, the carriers adhered to the surface, where the drug structure remained in crystalline form. Solvent-evaporated and surface-attached curcumin considerably improved drug solubility and dissolution compared to crude curcumin powder. In particular, solvent-evaporated solid dispersion provided a distinct enhancement in drug solubility (approximately 200,000-fold) and oral bioavailability. Therefore, this novel solvent-evaporated solid dispersion would be a promising candidate for oral pharmaceutical curcumin products. Chapter 2: The aim of this study was to develop a novel curcumin-loaded self-emulsifying drug delivery system (SEDDS) and a self-emulsifying granule system (SEGS) using two types of solid carriers to enhance the solubility and dissolution of the poorly water-soluble curcumin. The liquid SEDDS formula comprising Captex 355/Tween 80/Solutol HS15 at a volume ratio of 30/30/40 was selected because it had the smallest emulsion droplet size among all the liquid SEDDS formulations prepared. Curcumin (30 mg) was loaded into 1 ml of the liquid SEDDS. The curcumin-loaded liquid SEDDS (1 ml) was suspended in distilled water and then spray-dried with the solid carriers to produce two types of curcumin-loaded solid SEDDS formulations: HPMC and Neusilin were used as hydrophilic and mesoporous solid carriers, respectively. 1 g of HPMC or Neusilin was selected for the optimal solid SEDDS formulation due to its most improved dissolution. The SEGS was prepared with 1 ml of curcumin-loaded liquid SEDDS, 1 g HPMC or Neusilin, and 2 g Avicel using distilled water (100 ml) via a fluid bed granulator. The solid SEDDS prepared with HPMC or Neusilin showed irregular spherical shapes and smooth surface spherical shapes, respectively. In the SEGS prepared with HPMC, the liquid SEDDS and carriers might be attached to the surface of Avicel particles, whereas in the SEGS prepared with Neusilin, the liquid SEDDS might be attached to the surface of Avicel and Neusilin. The crystalline state of the drug was converted to an amorphous state in all the solid SEDDS and SEGS. All the formulations showed a significant improvement in drug solubility and dissolution compared with curcumin powder. The solid SEDDS and SEGS prepared with HPMC exhibited higher drug solubility and dissolution than those prepared with Neusilin. In particular, the solid SEDDS prepared with HPMC exhibited distinctly improved drug solubility and dissolution compared to the others. Thus, the solid SEDDS prepared using HPMC as a solid carrier has great potential for producing fine emulsions and improving the solubility and dissolution of curcumin.