Bioavailability of probucol from lipid and surfactant based formulations in minipigs: influence of droplet size and dietary state

Eur J Pharm Biopharm. 2008 Jun;69(2):553-62. doi: 10.1016/j.ejpb.2007.12.020. Epub 2008 Jan 3.

Abstract

The influence of droplet size on the absorption from lipid and surfactant based formulations was evaluated from two self-emulsifying formulations, a surfactant solution, and an oil solution. The self-emulsifying formulations was a self-emulsifying (SEDDS) and a self-nanoemulsifying (SNEDDS) formulation containing equal lipid and surfactant load, but exhibiting a large difference (approx 100 times) in the mean particle diameter of the resultant emulsion. The formulations were evaluated in a bioavailability study in fasted and fed Göttingen minipigs using probucol as model drug. In order to determine the bioavailability, an oil-in-water emulsion was included as i.v. formulation. The fasted group was fasted overnight and offered the first daily meal approx 4 h after treatment. The fed group was offered the first daily meal (50% energy from fat) 30 min prior to treatment. In the fasted group the SNEDDS exhibited a slightly faster absorption and higher bioavailability than the SEDDS, though non-significant. Furthermore, the bioavailability from the surfactant solution and the oil solution were slightly lower compared to the SNEDDS, indicating that both small particle size and digestibility are important in ensuring optimal bioavailability. Comparing the absorption in fasted and fed minipigs showed that probucol exhibited no significant food effect, when formulated in a lipid and surfactant based formulations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Animals
  • Anticholesteremic Agents / administration & dosage
  • Anticholesteremic Agents / pharmacokinetics*
  • Biological Availability
  • Caco-2 Cells
  • Chemistry, Pharmaceutical
  • Chromatography, High Pressure Liquid
  • Diet
  • Dietary Fats / pharmacology
  • Emulsions
  • Fasting / metabolism
  • Humans
  • Injections, Intravenous
  • Lipids / chemistry
  • Particle Size
  • Powders
  • Probucol / administration & dosage
  • Probucol / pharmacokinetics*
  • Surface-Active Agents
  • Swine
  • Swine, Miniature

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anticholesteremic Agents
  • Dietary Fats
  • Emulsions
  • Lipids
  • Powders
  • Surface-Active Agents
  • Probucol