Enhancement of the Solubility and Dissolution Rate of Rebamipide by Using Solid Dispersion Technique (Part I)

[摘要] Solid dispersion is an attractive tool of pharmaceutical technology used to improve the physical properties of drugs, among these properties is the solubility of the drugs. Rebamipide (REM) is used as potent antiulcer, mucoprotective drug, by stimulating the generation of prostoglandine enhanced mucosal protection. REM is a poorly soluble drug of class IV of biopharmaceutical classification system (BCS). In the present study, attempts were made to enhance solubility and dissolution rate of REM by solid dispersion technique. Thirty six REM formulas were prepared as a solid dispersion using different polymers include pluronic F-127 (poloxamer 407), polyethylene glycol 6000 (PEG6000), polyvinylpyrrolidon (PVP K30), and D-α-Tocopheryl polyethylene Glycol 1000 Succinate (TPGS) at different drug: polymer ratios (1:9, 1:12, and1:15) by using different preparation methods include solvent evaporation, fusion, and kneading method. The prepared formulas were characterized regarding drug content, production yield, solubility study, dissolution study, FTIR, DSC, PXRD, and SEM. The results indicate that the used polymer show improvement in drug solubility in the following descending order; TPGS>PVP K30>PEG 6000 > pluronic F-127 and the best drug: polymer ratio was 1:15 while best method was solvent evaporation. The optimum formula composes of drug: TPGS at ratio of 1:15 prepared by solvent evaporation shows 36.4 folds solubility enhancement compared to pure REM. The advance characterization of the selected formula indicates amorphousization of drug. It can be concluded that the solid dispersion technique is simple physical approach that can be followed to solve the problem of REM solubility using TPGS as hydrophilic carrier and best method is solvent evaporation method.

[学科分类] 计算机网络和通讯

[关键词] Rebamipide;Solid dispersion;TPGS.