Enhancing the oral bioavailability of baicalein via Solutol® HS15 and Poloxamer 188 mixed micelles system

J Pharm Pharmacol. 2019 May;71(5):765-773. doi: 10.1111/jphp.13058. Epub 2018 Dec 14.

Abstract

Objectives: To increase the solubility of baicalein (BAI) by preparing BAI-micelles (BAI-M) with Solutol HS15 (HS15) and Poloxamer 188 (F68), thereby improving its oral bioavailability.

Methods: Baicalein micelles were prepared with HS15 and F68 by thin-film dispersion method and optimized by central composite design (CCD) approach. Physicochemical, in vitro release, Caco-2 cell transport and pharmacokinetic studies of BAI-M were performed.

Key findings: The optimal formulation showed spherical shape by characterization of the transmission electron microscope with average small size (23.14 ± 1.46 nm) and high entrapment efficiency (92.78±0.98%) and drug loading (6.45±1.54%). The in vitro release study of BAI-M showed a significantly sustained release pattern compared with free BAI. Caco-2 cell transport study demonstrated that high permeability of BAI was achieved after loading it into micelles. Meanwhile, pharmacokinetics study of BAI-M showed a 3.02-fold increase in relative oral bioavailability compared with free BAI.

Conclusions: Based on our findings, we concluded that HS15 can be used as a carrier in this drug delivery system that includes F68, and BAI-M has great potential in improving solubility and oral bioavailability.

Keywords: Poloxamer 188; Solutol HS15; baicalein; micelles; oral bioavailability.

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Caco-2 Cells
  • Cell Line, Tumor
  • Drug Carriers / administration & dosage*
  • Drug Carriers / chemistry
  • Drug Carriers / pharmacokinetics*
  • Drug Delivery Systems / methods*
  • Drug Liberation
  • Flavanones / administration & dosage*
  • Flavanones / blood
  • Flavanones / chemistry
  • Flavanones / pharmacokinetics*
  • Humans
  • Male
  • Micelles
  • Particle Size
  • Permeability
  • Poloxamer / chemistry
  • Polyethylene Glycols / chemistry
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Solubility
  • Stearic Acids / chemistry

Substances

  • Drug Carriers
  • Flavanones
  • Micelles
  • Stearic Acids
  • Poloxamer
  • Polyethylene Glycols
  • baicalein
  • Solutol HS 15