Optimizing delivery of flurbiprofen to the colon using a targeted prodrug approach

The Journal of Pharmacy and Pharmacology
Anil K PhilipKamla Pathak

Abstract

The carboxylic group responsible for the gastric side-effects of the propionic acid derivative, flurbiprofen, was masked temporarily to overcome these side-effects and to accomplish colon-specific delivery of the drug. An amide prodrug (FLU-GLY) was synthesized by coupling flurbiprofen with L-glycine. Confirmation and characterization of the structure of the synthesized prodrug included elemental analysis, Fourier transform (FT)-IR, FT-NMR, mass (FAB) spectroscopy, and determinations of R(f), R(t) and R(M) values, respectively. Aqueous solubility and lipophilicity (logP) value were determined at pH 1.2, 4.0, 6.8 and 7.4. In-vitro reversion of FLU-GLY to flurbiprofen was measured at different pHs and in a simulated colonic environment. Acute toxicity and ulceration potential were evaluated in-vivo in albino rats. Pre-formulation studies showed increased hydrophilicity but a non-significant increase in lipophilicity of the prodrug. In-vitro reversion studies suggested that the prodrug remained intact until colonic pH was attained, when the colonic microfloral enzymes (amidase) hydrolysed the FLU-GLY amide linkage, releasing the free drug. In-vivo evaluation indicated that the prodrug was much less toxic and had less ulcerogenic a...Continue Reading

References

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Citations

Jun 8, 2010·Journal of Materials Science. Materials in Medicine·Saurabh VijayDipak K Majumdar
Dec 7, 2010·Journal of Materials Science. Materials in Medicine·Saurabh VijayDipak K Majumdar
Apr 1, 2010·Oman Medical Journal·Anil K Philip, Betty Philip
Nov 22, 2013·BioMed Research International·Sateesh Kumar Vemula, Vijaya Kumar Bontha
Aug 1, 2012·Journal of Drug Targeting·Prabhakar Reddy Veerareddy, Sateesh Kumar Vemula
Feb 9, 2016·Journal of Pharmaceutical Sciences·Lindi van ZylJoe Viljoen
Jun 12, 2014·European Journal of Drug Metabolism and Pharmacokinetics·Sateesh Kumar VemulaVenkat Ratnam Devadasu

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