title: 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.
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan, 712-749, South Korea.
authors.forename: Roshan
authors.initials: R
authors.lastname: Pradhan
authors.forename: Tuan Hiep
authors.initials: TH
authors.lastname: Tran
authors.forename: Ju Yeon
authors.initials: JY
authors.lastname: Choi
authors.forename: Im Soon
authors.initials: IS
authors.lastname: Choi
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
mesh_terms: D000409:Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D008297:Male; D015363:Quinolones / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D015363:Quinolones; C052785:rebamipide; D000409:Alanine