Medicinal Chemistry Research

, Volume 23, Issue 1, pp 503–517

Novel ibuprofen prodrugs with improved pharmacokinetics and non-ulcerogenic potential

  • Valmik D. Dhakane
  • Hemant V. Chavan
  • Vishnu N. Thakare
  • Laxman K. Adsul
  • Sadanand N. Shringare
  • Babasaheb P. Bandgar
Original Research

DOI: 10.1007/s00044-013-0639-8

Cite this article as:
Dhakane, V.D., Chavan, H.V., Thakare, V.N. et al. Med Chem Res (2014) 23: 503. doi:10.1007/s00044-013-0639-8

Abstract

In the present study, we evaluated the anti-inflammatory activity with pharmacokinetic, ulcerogenic properties of various synthesized prodrugs of ibuprofen in experimental animals. Prodrugs 2, 6, 9, 10, 12, and 14 were found to possess significant anti-inflammatory activity with almost non-ulcerogenic potential than standard drug ibuprofen 1a in both normal and inflammation-induced rats. Metabolic stability of prodrugs 2, 6, 9, 10, 12, and 14 were also studied in rat liver microsomes and oral bioavailability was determined by estimating area under curve (AUC) and plasma concentration of these prodrugs at various time intervals. The experimental findings elicited higher AUC and plasma concentration at 1 and 2 h indicating improved oral bioavailability as compared to parent ibuprofen. These prodrugs are found to have least gastric ulceration with retain anti-inflammatory activity observed in experimental animals. Therefore, present experimental findings demonstrated significant improvement of various pharmacokinetic properties with least ulcerogenic potential of ester prodrugs of ibuprofen an anti-inflammatory agent

Keywords

ProdrugIbuprofenAnti-inflammatory activityNon-ulcerogenicPharmacokinetic properties

Abbreviations

NSAID

Nonsteroidal anti-inflammatory drug

Tris–HCl

Tris(hydroxymethyl)aminomethane hydrochloride

NADPH

Nicotinamide adenine dinucleotide phosphate

HPLC

High performance liquid chromatography

GC

Gas chromatography

RLM

Rat liver microsomes

RP

Rat plasma

API

Active pharmaceutical ingredient

UI

Ulcer index

GI

Gastrointestinal

DMAc

Dimethyl acetamide

PTSA

p-Toluene sulfonic acid

PXRD

Powder X-ray diffraction

RT

Room temperature

TMG

1,1,3,3-Tetramethyl guanidine

18 Crown 6

1,4,7,10,13,16-Hexaoxacyclooctadecane

EP

European pharmacopoeia

Ar

Aromatic

BDL

Below detection limit

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Valmik D. Dhakane
    • 1
  • Hemant V. Chavan
    • 1
  • Vishnu N. Thakare
    • 2
  • Laxman K. Adsul
    • 1
  • Sadanand N. Shringare
    • 1
  • Babasaheb P. Bandgar
    • 1
  1. 1.Medicinal Chemistry Research Laboratory, School of Chemical SciencesSolapur UniversitySolapurIndia
  2. 2.Department of PharmacologySinhgad Institute of Pharmaceutical SciencesLonavalaIndia