Development and evaluation of a gastro-retentive delivery system for improved antiulcer activity of ginger extract (Zingiber officinale)

Abstract

Aim was to develop and optimize multiunit gastro-retentive floating beads (FBs) intended for localized and prolonged release of ginger for treating gastric ulcers. Protective effect of ginger extract (GE) against ulcer is well documented, but therapeutic use is compromised due to poor bioavailability and physicochemical properties. GE was only slightly soluble (3.19 ± 0.38 mg/ml) in simulated gastric fluid (SGF; pH 1.2). The solubility decreased in water to 0.69 ± 0.03 mg/ml and further by 26% in the presence of calcium carbonate (0.5% w/v). We prepared FBs of GE using calcium carbonate and sodium alginate in different proportions. Beads were evaluated for diameter, buoyancy, entrapment, and porosity. In vitro dissolution showed a Fickian release with a cumulative release of >80% at 24 h. Preclinical evaluation was done in cold-restraint stress induced gastric ulcers, in albino rats, in terms of (i) ulcer index, hemorrhagic streaks (l), mucus content, (ii) oxido-nitrosative stress, and (iii) histopathology. GE loaded FBs (200 mg/kg) were significantly better than free GE and better/equivalent to cimetidine (10 mg/kg). The system was evaluated for therapeutic effect (curative), i.e. after the induction of ulcers. Most of the natural phytochemical or antioxidants show pretreatment effectiveness. We, however, developed and established GE FBs for sustained curative effect.