Diglyceride prodrug strategy for enhancing the bioavailability of norfloxacin

[Display omitted] ► Design, kinetics and evaluation of norfloxacin prodrug in renal abscess model. ► Derivatization of carboxylic group instead of piperazine nitrogen of norfloxacin. ► Dipalmitin explored as a carrier to improve oral bioavailability. ► Prodrug exhibited enhanced bioavailability and longer duration than norfloxacin. Prodrug approach using diglyceride as a promoiety is a promising strategy to improve bioavailability of poorly absorbed drugs and the same was explored in the present work to improve oral bioavailability of norfloxacin; a second generation fluoroquinolone antibacterial. The prodrug was synthesized by standard procedures using dipalmitine as a carrier and the structure was confirmed by spectral analysis. Higher Log P indicated improved lipophilicity. The ester linkage between norfloxacin and dipalmitine would be susceptible to hydrolysis by lipases to release the parent drug and carrier in the body. In vivo kinetic studies in rats indicated 53% release of norfloxacin in plasma at the end of 8 h. The prodrug exhibited improved pharmacological profile than the parent compound at equimolar dose that indirectly indicated improved bioavailability.