Enhanced oral bioavailability of piperine by self-emulsifying drug delivery systems: in vitro, in vivo and in situ intestinal permeability studies

Drug Deliv. 2015;22(6):740-7. doi: 10.3109/10717544.2014.898109. Epub 2014 Mar 27.

Abstract

The main purpose of this work was to develop and evaluate a self-emulsifying drug delivery system (SEDDS) of piperine to enhance its solubility and bioavailability. The formulation was optimized by solubility test and ternary phase diagrams. Then physiochemical properties and in vitro release of SEDDS were characterized. In vivo pharmacokinetics study and in situ single-pass intestinal perfusion were performed to investigate the effects of SEDDS on the bioavailability and intestinal absorption of piperine. The optimized formulation was composed of ethyl oleate, Tween 80 and Transcutol P (3:5.5:1.5, w/w), with the level of the piperine reached 2.5% (w/w). The in vitro dissolution rates of piperine SEDDS were significantly higher than the self-prepared capsules. In vivo pharmacokinetic study showed Cmax1, Cmax2 and area under the curve of piperine after oral administration of SEDDS in rats were 3.8-, 7.2- and 5.2-fold higher than the self-prepared capsules, respectively, and the relative bioavailability of SEDDS was 625.74%. The in situ intestinal absorption study revealed that the effective permeability and the effective absorption rate values of piperine for SEDDS were significantly improved comparing to solutions (p < 0.01). So SEDDS formulation could improve the oral bioavailability and intestinal absorption of piperine effectively.

Keywords: Bioavailability; dissolution; piperine; self-emulsifying drug delivery system; single-pass intestinal perfusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Alkaloids / administration & dosage*
  • Alkaloids / pharmacokinetics*
  • Animals
  • Area Under Curve
  • Benzodioxoles / administration & dosage*
  • Benzodioxoles / pharmacokinetics*
  • Biological Availability
  • Chemistry, Pharmaceutical
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems / methods*
  • Drug Liberation
  • Emulsifying Agents / chemistry
  • Emulsions / chemistry*
  • Intestinal Absorption
  • Lipids / chemistry
  • Male
  • Piperidines / administration & dosage*
  • Piperidines / pharmacokinetics*
  • Polyunsaturated Alkamides / administration & dosage*
  • Polyunsaturated Alkamides / pharmacokinetics*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Alkaloids
  • Benzodioxoles
  • Emulsifying Agents
  • Emulsions
  • Lipids
  • Piperidines
  • Polyunsaturated Alkamides
  • piperine