The Crystal Form And Bioavailability Research Of Rebamipide

Polymorphic drug are made from crystalline state pharmaceutical material, and are referred to the active pharmaceutical ingredient(API) of the solid drugs exiting in a specific crystalline state. Crystalline drug is solid drug, which can improve its physical and chemical properties, such as the melting point, solubility, and then improve the bioavailability of API.Rebamipide is a drug for treatment of gastric ulcer and acute or chronic gastritis, with a low oral bioavailability(about 10%) due to its poor aqueous solubility. In order to improve its solubility, improving drug absorption, we designed and synthesized five pharmaceutical crystallines: Na2(H2O)4(Reb)(1),(HReb)(CH3NH2CH3)[(CH3)2CHOH](2), H2Reb·CH3OH(3), H2Reb·(DMSO)2(4) as well as methyl ester HReb-CH3(5).The structure of compounds 1-5 have been thoroughly characterized by X-ray single crystal diffraction, infrared spectrum, thermogravimetry and differential scanning calorimetry. The reported sodium salt [Na(CH3CH2OH)(HReb)](6) was prepared. The synthesis of compounds 1 and 6 was controlled by temperature and the formation of 3 and 5 was controlled by solubility. The dissolution studies display that the maximum solubility of compounds 1, 3, 5 in the HCl solution with pH = 1.2 have been improved. Furthermore, pharmacokinetic behavior of compounds 1, 3, 5 and API was investigated and the study revealed that compounds 3 and 5 possessed an improved pharmacokinetic profile.The study on polymorphic drugs has promising application. Novel crystalline forms prepared in this research with obviously increased bioavailability have provided powerful technical support for the medicament development of Rebamipide.