SYNTHESIS AND CHARACTERIZATION OF NOVEL AMINO ACID PRODRUG OF GLICLIZIDE
Diabetes is a metabolic disorder which has emerged as a major healthcare threat throughout the world. Gliclazide is an extensively used sulphonyl urea compound in the treatment of diabetes. As per BCS classification gliclazide is categorized under class II drug which do have poor solubility. Limited aqueous solubility is a major pharmacokinetic barrier in development of new drug entity for discovery focused pharmaceutical companies. Prodrugs are recognized and well known concept to overcome pharmacokinetic barriers like poor solubility. Solubility enhancement is an important parameter for increasing the bioavailability. Hence the objective of the investigation was to improve the aqueous solubility and in turn bioavailability by synthesis of novel amino acid prodrug of Gliclazide. Characterization of prepared prodrug was done by IR, NMR, Mass and DSC. In vitro chemical hydrolysis profiles revealed that the synthesized amino acid derivatives of Gliclazide are chemically stable in Simulated Gastric fluid pH 1.2 and simulated Intestinal fluid pH 7.2. Decrease in Log P value, 0.41 of amino acid prodrug compared to 2.52 of Gliclazide indicates the increase in hydrophilic property of synthesized amino acid derivatives of Gliclazide. In silico analysis was done for synthesized prodrugs by ChemBio3D ultra 11.0 software