Enhanced bioavailability of probucol following the administration of solid dispersion systems of probucol-polyvinylpyrrolidone in rabbits

Biol Pharm Bull. 2009 Nov;32(11):1880-4. doi: 10.1248/bpb.32.1880.

Abstract

Disks of probucol and solid dispersion systems of probucol-polyvinylpyrrolidone (PVP) in various weight ratios were prepared. Dissolution of probucol was markedly increased in the solid dispersion systems in J.P. XV disintegration media No. 1 (pH 1.2) and No. 2 (pH 6.8). The concentrations of probucol after the dissolution of the disks of solid dispersion systems showed supersaturation. Following the administration of disks of solid dispersion systems in rabbits, a marked increase in the area under the plasma concentration time curve (AUC) was observed. When the weight ratio of PVP to probucol was larger, a larger AUC was observed. When disks of the 1 : 9 solid dispersion system (weight ratio of probucol : PVP=1 : 9) containing 50 and 100 mg probucol were respectively administered, AUC values were approximately proportional to the dose. AUC values following the administration of disks of the 1 : 9 solid dispersion systems containing 15 mg probucol (total weight: 150 mg) and 500 mg probucol were approximately equal. The mean half life (t(1/2)) was 12 h when disks of the 1 : 9 solid dispersion system were administered, whereas the t(1/2) was 35 h when probucol disks were administered. The markedly increased dissolution of probucol in solid dispersion systems resulted in a marked increase in its bioavailability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Anticholesteremic Agents / administration & dosage
  • Anticholesteremic Agents / blood
  • Anticholesteremic Agents / pharmacokinetics*
  • Area Under Curve
  • Biological Availability
  • Male
  • Povidone / administration & dosage*
  • Probucol / administration & dosage
  • Probucol / blood
  • Probucol / pharmacokinetics*
  • Rabbits
  • Solubility

Substances

  • Anticholesteremic Agents
  • Povidone
  • Probucol