Enhanced oral bioavailability of etodolac by self-emulsifying systems: in-vitro and in-vivo evaluation

J Pharm Pharmacol. 2010 Feb;62(2):173-80. doi: 10.1211/jpp.62.02.0004.

Abstract

Objectives: The objective of this study was to prepare a self-emulsifying drug delivery system (SEDDS) for oral bioavailability enhancement of a poorly water-soluble drug, etodolac. The SEDDS formulations were optimized by evaluating their ability to self-emulsify when introduced to an aqueous medium under gentle agitation, and by determination of the particle size of the resulting emulsion.

Methods: An optimized formulation of SEDDS (composed of 20% etodolac, 30% oil Labrafac WL1349, 10% Lauroglycol 90 and 40% Labrasol) was selected for bioavailability assessment in rabbits. The anti-inflammatory effect was also determined in rats, and compared with powder drug and etodolac suspension in water (50 mg/kg).

Key findings: The peak plasma concentration of 16.4 +/- 1.1 microg/ml appeared after 1.3 +/- 0.2 h, whereas with powder drug and etodolac suspension the values were 7.5 +/- 0.5 and 10.6 +/- 0.7 microg/ml at 4.2 +/- 0.4 and 2.4 +/- 0.2 h, respectively. The AUC(0-8) of the etodolac SEDDS formulation was 2.3 times that of the pure drug and 1.4 times that of the suspension form. SEDDS formulation exhibits a 21% increase in paw thickness compared with a 39% increase on oral administration of etodolac suspension after 4 h at the same dose of the drug (20 mg/kg).

Conclusions: The result indicates the utility of SEDDS for the oral delivery of etodolac and potentially other lipophilic drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption
  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Biological Availability
  • Chromatography, High Pressure Liquid
  • Drug Compounding
  • Drug Delivery Systems / methods*
  • Edema / drug therapy
  • Emulsions
  • Etodolac / administration & dosage*
  • Etodolac / chemistry
  • Etodolac / pharmacokinetics*
  • Etodolac / therapeutic use
  • Male
  • Particle Size
  • Powders
  • Rabbits
  • Rats
  • Rats, Wistar
  • Solubility
  • Suspensions

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Emulsions
  • Powders
  • Suspensions
  • Etodolac