Prepration And Evalution Of Colon Targated Prodrug Of Etodolac: Colon Targated Prodrug Of Etodolac

In the present study carboxylic group of Etodolac, responsible for gastric side effects, was masked temporarily not only to overcome the side effects but also to achieve colon specific delivery. Amide prodrug (Etodolac-glycine conjugate) was synthesized by coupling Etodolac with glycine The synthesized prodrug was characterized by melting point, thin layer chromatography, RM values, scanning electro microscopy, x-ray diffraction crystallography and High performance liquid chromatography. The synthesized prodrug’s structure was confirmed by elemental analysis, Fourier transform infrared spectroscopy, Fourier transform nuclear magnetic resonance spectroscopy and mass spectroscopy. Aqueous solubilities and lipophilicity (log P) values were determined at different pH media namely HCl buffer pH 1.2, acid phthalate buffer pH 4.0, phosphate buffer pH 6.8 and pH 7.4. In vitro reversion of Etodolac-glycine conjugate to Etodolac was done at different pH including colonic environment. Preformulation studies showed increased aqueous solubility however no significant change was observed in lipophilicity of the prodrug compared to Etodolac. X-ray diffraction crystallography of the prodrug showed reduced crysatllanitiy than Etodolac and supported the increased solubility. In vitro reversion, showed prodrug to remain intact in all the other tested pH except colonic pH, where the colonic microfloral enzymes (amidase) hydrolyzed Etodolac-glycine conjugate amide linkage, releasing the free drug.