Worrawee Siripruekpong

Curcumin and resveratrol are polyphenolic compounds that have been shown to exhibit synergistic therapeutic properties including anti-inflammatory, anticancer, and antiulcer activities, which may be exploited for the treatment of gastric diseases. However, both compounds have poor aqueous solubility and rapid metabolism, resulting in a low oral bioavailability. In situ gelling, liquid formulations were developed to produce a gastroretentive, raft-forming delivery vehicle to improve bioavailability. Solid dispersions containing a mixture of curcumin and resveratrol with Eudragit^® EPO (Cur/Res-SD) were first prepared using solvent evaporation, to improve the solubility and dissolution of the compounds. Solid dispersions of a weight ratio of 1:10 curcumin/resveratrol to Eudragit^® EPO were subsequently incorporated into in situ gelling, liquid formulations based on the gelling polymers, sodium alginate (low viscosity and medium viscosity), pectin, and gellan gum, respectively. Calcium carbonate and sodium bicarbonate were included to produce carbon dioxide bubbles in the gel matrix, on exposure to gastric fluid, and to achieve flotation. Moreover, the calcium ions acted as a crosslinking agent for the hydrogels. Optimized formulations floated rapidly (<60 s) in simulated gastric fluid (pH = 1.2) and remained buoyant, resulting in the gradual release of more than 80% of the curcumin and resveratrol content within 8 h. The optimized formulation based on medium-viscosity sodium alginate exhibited enhanced cytotoxic activity toward human gastric adenocarcinoma cell lines (AGS), compared with unformulated curcumin and resveratrol compounds, and increased anti-inflammatory activity against RAW 264.7 macrophage cells compared with the NSAID, indomethacin. These findings demonstrate that in situ gelling, liquid formulations, loaded with a combination of curcumin and resveratrol in the form of solid dispersions, show potential as gastroretentive delivery systems for local and systemic effects.

Curcumin, a polyphenolic extract from the rhizomes of turmeric, exhibits antioxidant, anti-inflammatory, and anticancer activities, which are beneficial for the treatment of gastric diseases. However, curcumin’s therapeutic usefulness is restricted by its low aqueous solubility and short gastric residence time. In this study, curcumin-loaded solid dispersion (ratio 1:5) was prepared using Eudragit^® EPO (Cur EPO-SD), resulting in an approximately 12,000-fold increase in solubility to 6.38 mg/mL. Expandable films incorporating Cur EPO-SD were subsequently prepared by solvent casting using different types of starch (banana, corn, pregelatinized, and mung bean starch) in combination with chitosan. Films produced from banana, corn, pregelatinized and mung bean starch unfolded and expanded upon exposure to simulated gastric medium, resulting in sustained release of 80% of the curcumin content within 8 h, whereas films based on pregelatinized starch showed immediate release characteristics. Curcumin-loaded expandable films based on different types of starch exhibited similar cytotoxic effects toward AGS cells and more activity than unformulated curcumin. Furthermore, the films resulted in increased anti-inflammatory activity against RAW 264.7 macrophage cells compared with the NSAID, indomethacin. These findings demonstrate the potential of expandable curcumin-loaded films as gastroretentive dosage forms for the treatment of gastric diseases and to improve oral bioavailability.