Abstract

SYNTHESIS AND EVALUATION OF SOME AMINO ACID CONJUGATES OF KETOPROFEN

Prof. Ashish Nandakumar Phuge*

ABSTRACT

The emphasis of present research work is to improve solubility behavior of NSAIDs by different amino acid conjugation. Present conjugate approach stands for modification to overcome pharmaceutical barriers like solubility behavior. The prodrugs designed by classical approach increase lipophilicity of the drug, which decreases the water solubility thus decreasing the concentration gradient, which controls drug absorption. To overcome the limitations of traditional prodrug approach, water soluble conjugates are designed by adding selected amino acid to the drug moiety that are the substrates for the enzyme located at the intestinal brushborder. Amino acid conjugate of ketoprofen was synthesized by conventional coupling method and it was characterized by Melting Point, TLC, UV, IR, NMR and Mass Spectroscopy. Serine - Ketoprofen conjugate has maximum water solubility. Present research work indicates that conjugates synthesized with amino acid possess more water solubility. From the pH rate profile it was found that all the synthesized compounds, are stable at low pH values (pH 1.2), while undergo hydrolysis as the pH is increased (pH 7.4). This indicates that the synthesized compounds will be hydrolyzed and subsequently absorbed through intestine. In future this approach can be applied to other NSAIDs having free carboxyl functional group as well as in vivo bioavailability study can be undertaken in animals and can be correlated in humans.

Keywords: Ketoprofen, Prodrug, Conjugates, Synthesis.