Abstract
Curcumin and resveratrol are naturally occurring polyphenolic compounds, showing synergistic potential in treatment of several chronic disorders. However, their poor oral bioavailability, which is primarily due to limited aqueous solubility, is a major hurdle in tapping their synergistic potential for therapeutic purposes. Cyclodextrins are oligosaccharides which shield hydrophobic functionalities and enhance aqueous solubility of compounds. The objective of present research was to prepare and characterize curcumin-resveratrol-cyclodextrin amorphous ternary systems, for simultaneous dissolution enhancement of both drugs. |Ultraviolet-Visible (UV-Vis) spectroscopy method was developed for simultaneous quantification of drugs. Alpha(α)-cyclodextrin, beta(β)–cyclodextrin, gamma(γ)–cyclodextrin and hydroxyl propyl beta(HPβ)–cyclodextrin were screened for their apparent aqueous solubility enhancement ability for curcumin and resveratrol. HPβ–cyclodextrin was found to be most effective. Solid dispersions in molar ratios of 1:1:2 (curcumin:resveratrol:each cyclodextrin), were prepared using solvent evaporation method and characterized by light microscopy, scanning electron microscopy(SEM), thermogravimetric analysis(TGA), modulated differential scanning calorimetry(MDSC), X-ray powder diffraction(XRPD), infrared(IR) spectroscopy, and Raman spectroscopy. Solid dispersions appeared to have irregular morphology and optimum thermal stability. Both drugs showed sharp melting peaks which disappeared in HPβ-cyclodextrin based solid dispersion, indicating reduction in their crystallinity. XRPD study showed HPβ-cyclodextrin based solid dispersion was amorphous in nature. IR spectroscopy indicated H-bonding between drugs and cyclodextrin, Raman spectroscopy indicated shielding of drugs by cyclodextrin cavity. Dissolution of HPβ-cyclodextrin based solvent evaporated solid dispersion and corresponding physical mixture was carried out in USP type II apparatus with phosphate buffer pH 7.4. Within 30 minutes, dissolution enhancement of 2.4 fold was achieved for curcumin via solid dispersion compared to physical mixture, 55.3% of resveratrol was released from solid dispersion compared to 23.3% from physical mixture. |Solid dispersions of curcumin and/or resveratrol and HPβ-cyclodextrin were prepared by freeze drying using acetone:water, water solvent systems, and characterized. Dissolution study showed that within 5 minutes, 98% of curcumin and 100% of resveratrol were released from acetone:water based solid dispersion. |Thus, HPβ-cyclodextrin based solid dispersion appeared effective for simultaneous dissolution enhancement of curcumin and resveratrol. Freeze drying emerged as more suitable method owing to limited use of organic solvents. In-vitro efficacy of solid dispersions should be explored in future.