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

Roshan Pradhan, Tuan Hiep Tran, Ju Yeon Choi, Im Soon Choi, Han-Gon Choi, Chul Soon Yong, Jong Oh Kim

Index: Arch. Pharm. Res. 38(4) , 522-33, (2015)

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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.