Formulation of solid dispersion of rebamipide evaluated in a rat model for improved bioavailability and efficacy

• Published in: Journal of pharmacy and pharmacology 2011-12, Vol.63 (12), p.1539-1547
• Main Authors: Tung, Nguyen-Thach, Park, Chun-Woong, Oh, Tack-oon, Kim, Ju-Young, Ha, Jung-Myung, Rhee, Yun-Seok, Park, Eun-Seok
• Format: Article
• Language: English
• Subjects: Alanine - administration & dosage; Alanine - analogs & derivatives; Alanine - chemistry; Alanine - pharmacokinetics; Algorithms; Animals; Anti-Ulcer Agents - administration & dosage; Anti-Ulcer Agents - chemistry; Anti-Ulcer Agents - pharmacokinetics; Area Under Curve; Biological Availability; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Half-Life; Male; pharmacodynamic; pharmacokinetic; Quinolones - administration & dosage; Quinolones - chemistry; Quinolones - pharmacokinetics; Rats; Rats, Sprague-Dawley; rebamipide; solid dispersion; Solubility; Solvents; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1111/j.2042-7158.2011.01360.x

Objectives  Rebamipide, a novel anti‐ulcer agent, is listed in biopharmaceutics classification class IV because of its low aqueous solubility and permeability. Consequently, the bioavailability of rebamipide is under 10% in humans. The aim of this study was to increase the solubility and determine the effect of solubility enhancement on the bioavailability and efficacy of rebamipide (RBM). Methods  After taking into account the physiochemical properties of RBM (solubility, melting point, dosage etc.), solid dispersion was chosen as the solubility enhancement method. A rebamipide solid dispersion system containing the drug, l‐lysine, PVP‐VA 64 and poloxamer 407 was obtained from a spray‐drying method. Solubility enhancement of RBM from the solid dispersion was determined by a dissolution test in 900 ml at pH 1.2. The bioavailability and efficacy of RBM solid dispersion were evaluated in a rat model. Key findings  The aqueous solubility of RBM was improved 62.17 times by solid dispersion. The oral bioavailability of the drug was also increased 1.74‐fold from solid dispersion compared with the reference product in a rat model. With regard to the anti‐ulcer effect, the percentage inhibition of the solid dispersion was 2.71 times higher than that of the reference product in the ulcer‐induced rat model. Conclusions  A solid dispersion of rebamipide was successfully formulated using the spray‐drying method. Bioavailability and efficacy of rebamipide were increased significantly by solubility enhancement of the drug.