title: Synthesis, Characterization and Antimicrobial Evaluation of Lipid Based Norfloxacin Prodrug.
abstract: BACKGROUND
  Fluoroquinolones, the synthetic antibacterial agents are being successfully utilized against bacterial infections, since the time immemorial. Despite of enormous useful features, these drugs are associated with some limitations also. Large number of efforts has been made by various scientists to improve pharmacokinetic properties of these drugs and hence, to overcome the limitations associated with them.
  
  
  OBJECTIVE
  The aim of this paper is to introduce a novel scheme for synthesis of prodrug with improved pharmacokinetic properties i.e., lipophilicity and consequently, modified bioavailability of norfloxacin.
  
  
  METHODS
  Fatty acid hydrazide of selected fatty acid was synthesized followed by preparation of 5-formyl salicylamide. N-Mannich base of norfloxacin was synthesized by reacting norfloxacin with 5-formyl salicylamide. The prodrug was obtained by covalently coupling this N-Mannich base of norfloxacin with fatty acid hydrazide. The synthesized lipid based prodrug was evaluated for partition coefficient by shake flask method and screened for antimicrobial activity against selected strains. Drug content determination and in vitro dissolution studies utilizing HPLC were also carried out.
  
  
  RESULTS
  The synthesized prodrug was found to exhibit improved partition coefficient (1.15) when compared with parent drug, norfloxacin (0.46). The results of antimicrobial evaluation indicate promising antibacterial and antifungal activity.
  
  
  CONCLUSIONS
  The synthesized prodrug proved to be a good antimicrobial substance due to improved lipophilicity and would be expected to be used as a suitable candidate for exploration of possible utilities in treatment of bacterial infections in forthcoming time.
authors.affiliation: Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra-136119, India.
authors.forename: Prabodh Chander
authors.initials: PC
authors.lastname: Sharma
authors.affiliation: Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra-136119, India.
authors.forename: Mona
authors.initials: M
authors.lastname: Piplani
authors.affiliation: Institute of Pharmaceutical Sciences, Guru Ghasidas University, Bilaspur-495009, India.
authors.forename: Harish
authors.initials: H
authors.lastname: Rajak
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D000935:Antifungal Agents / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D024841:Fluoroquinolones / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D009643:Norfloxacin / Q000737:chemistry* / Q000493:pharmacokinetics; D011355:Prodrugs / Q000737:chemistry* / Q000493:pharmacokinetics; D012457:Salicylamides / Q000737:chemistry; D012995:Solubility / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D024841:Fluoroquinolones; D008055:Lipids; D011355:Prodrugs; D012457:Salicylamides; C031060:salicylamide; D009643:Norfloxacin
keywords: Antibacterial; bioavailability; drug release; fatty acid; partition coefficient; prodrug.