Development of a rebamipide solid dispersion system with improved dissolution and oral bioavailability.

Abstract

The purpose of this study was to improve the gastric solubility and bioavailability of rebamipide (RBM) by preparing the RBM solid dispersion tablet (RBM-SDT) from solid dispersion powder prepared by spray-drying technique. For preparation of rebamipide solid dispersions (RBM-SDs), solubility study was performed in various hydrophilic carriers and alkalizers, among which sodium alginate and sodium carbonate were selected as the hydrophilic polymer and alkalizer, respectively. Different combinations of drug-polymer-alkalizer were dissolved in aqueous solution and spray-dried in order to obtain solid dispersions. Noticeable improvement in aqueous solubility (approximately 200 times) and in vitro dissolution rate was observed by RBM-SDs, compared to RBM powder. The optimized formulation of RBM-SD powder consisted of RBM powder/sodium alginate/sodium carbonate at the weight ratio of 1/2/2. The transformation of crystalline RBM to amorphous RBM-SD powder was clearly demonstrated by powder X-ray diffraction, differential scanning calorimetry (DSC) and scanning electron microscopy. The optimized RBM-SD was formulated in tablet dosage form, containing approximately 2% sodium lauryl sulphate and poloxamer F68 as wetting agents. The RBM-SDT exhibited enhanced dissolution in hydrochloric acid buffer (pH 1.2) and distilled water. Moreover, pharmacokinetic study in rats showed higher AUC and Cmax for RBM-SDT than those for RBM powder and commercial product. Thus, the developed RBM-SDT formulation can be more efficacious for improving oral bioavailability of RBM.