A new strategy for enhancing the oral bioavailability of drugs with poor water-solubility and low liposolubility based on phospholipid complex and supersaturated SEDDS

PLoS One. 2013 Dec 31;8(12):e84530. doi: 10.1371/journal.pone.0084530. eCollection 2013.

Abstract

A novel supersaturated self-emulsifying drug delivery system (Super-SEDDS) loaded with scutellarin-phospholipid complex (SPC) was developed. The system aimed to address the limitations presented by conventional SEDDS as delivery carriers for drugs with poor water-solubility, low liposolubility and high dose. As an intermediate, SPC was first prepared based on the response surface design. The presence of amorphous scutellarin was demonstrated through differential scanning calorimetry (DSC) and X-ray diffraction (XRD), while enhanced liposolubility was confirmed through comparison with scutellarin powder via an octanol/water distribution test. On the basis of the solubility study and ternary phase diagram, Super-SEDDS containing SPC of up to 200% equilibrium solubility (Seq) was designed, which composed of ethyl oleate, Cremophor RH40 and Transcutol HP with a ratio of 60:25:15 (w/w%). The subsequent in vitro lipolysis study and ex vivo intestinal absorption test indicated that Super-SEDDS enhanced the cumulative dissolution from 70% to 100% and improved the intestinal absorption from 0.04 to 0.12 µg/cm(2) compared with scutellarin powder. Furthermore, an in vivo study demonstrated that Super-SEDDS achieved the AUC0-t of scutellarin up to approximate 1.7-fold as scutellarin powder. It was also proved superior to SPC and the conventional SEDDS. Super-SEDDS showed great potential for expanding the usage of SEDDS and could act as an alternative to conventional SEDDS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral*
  • Apigenin / chemistry*
  • Biological Availability*
  • Calorimetry, Differential Scanning
  • Drug Delivery Systems / methods*
  • Emulsifying Agents / chemistry*
  • Ethylene Glycols
  • Glucuronates / chemistry*
  • Humans
  • Molecular Structure
  • Pharmaceutical Preparations / administration & dosage
  • Pharmaceutical Preparations / chemistry*
  • Phospholipids / chemistry*
  • Polyethylene Glycols
  • Solubility
  • X-Ray Diffraction

Substances

  • Emulsifying Agents
  • Ethylene Glycols
  • Glucuronates
  • Pharmaceutical Preparations
  • Phospholipids
  • scutellarin
  • cremophor
  • Polyethylene Glycols
  • Apigenin
  • carbitol

Grants and funding

This work was financially supported by the Special Project on the Integration of Industry Education Research of Guangdong Province (No. 2009B090300321), the Science and Technology Development Fund of Macao Special Administrative Region (No. 094/2012/A3) and the National High Technology Research and Development Program of China (No. 2012AA022704). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.