Raft-forming gastro-retentive formulations based on Centella asiatica extract-solid dispersions for gastric ulcer treatment.

Liquid raft-forming formulations comprising solid dispersions of glycoside-rich Centella asiatica extract and Eudragit® EPO (GR-SD) were developed to achieve prolonged delivery of the glycosides, asiaticoside (AS) and madecassoside (MS) in the stomach and thus increase the effectiveness of gastric ulcer treatment. Solid dispersions of GR extract and Eudragit® EPO (GR-SD, weight ratio 1:0.5) resulted in the highest solubility of AS (41.7 mg/mL) and MS (29.3 mg/mL) and completed dissolution of both glycosides occurred in SGF within 10 min. The optimized raft-forming formulation was composed of alginate (2%), HPMC K-100 (0.5%), GR-SD (1.2%), and calcium carbonate (0.5%) as a calcium source and carbon dioxide producer. The formulation provided sufficient raft strength (> 7.0 g), rapid floating behavior in SGF (~30 s), and sustained release of AS (more than 80%) and MS (85%) over 8 h. GR-SD-based formulations administered once daily to rats for two days at a dose of 10 mg AS/kg reduced the severity of gastric ulcer induced by indomethacin with a greater curative efficacy than those of unformulated GR extract and a standard antiulcer agent: lansoprazole (p < 0.05). These findings demonstrate that GR-SD-based raft-forming systems offer significant promise for improving the treatment of gastric ulcers induced by non-steroidal anti-inflammatory drugs.

Strategies for Improving Healing of the Gastric Epithelium Using Oral Solid Dispersions Loaded with Pentacyclic Triterpene-Rich Centella Extract.

The pentacyclic triterpenoid compounds in Centella asiatica extract, mainly consisting of asiaticoside (AS), asiatic acid (AA), madecassoside (MS), and madecassic acid (MA), possess wound healing and anti-ulcer properties, but their low aqueous solubility and dissolution rate are disadvantageous for oral administration. In this study, pentacyclic triterpene-rich centella extract (PRE) was combined with Eudragit® EPO as a hydrophilic polymer using solvent evaporation to produce a solid dispersion (PRE-ESD). The optimum PRE/Eudragit ratio of 1:2 enhanced the solubility and dissolution of glycosides (AS > 3.5 folds, MS > 2 folds) and aglycones (AA > 65 folds and MA > 56 folds) in 0.1 N hydrochloric acid (pH 1.2). DSC, XRD, and FT-IR analysis showed that the four pentacyclic triterpenes in PRE existed in the amorphous state in the solid dispersion. Moreover, almost 100% of the compounds were released from the solid dispersion within 2 h. The effects of PRE-ESD on cell proliferation and wound healing in vitro were investigated in human gastric epithelial cell lines (AGS cells). Exposure to PRE-ESD (equivalent to PRE concentration of 10 µg/mL) promoted cell proliferation and enhanced 'wound closure' in the scratch assay of wound healing by 82% compared with non-treated groups. Unformulated MA and AA aglycones did not exhibit a wound healing effect. Moreover, PRE-ESD was found to accelerate wound closure compared with either AS or MS, indicating that the wound healing properties of PRE-ESD are conferred by the active compounds AS and MS that are presented in PRE.