Mixed micelles loaded with silybin-polyene phosphatidylcholine complex improve drug solubility

Acta Pharmacol Sin. 2011 Jan;32(1):108-15. doi: 10.1038/aps.2010.192. Epub 2010 Dec 20.

Abstract

Aim: To prepare a novel formulation of phosphatidylcholine (PC)-bile salts (BS)-mixed micelles (MMs) loaded with silybin (SLB)-PC complex for parenteral applications.

Methods: SLB-PC-BS-MMs were prepared using the co-precipitation method. Differential scanning calorimetry (DSC) analysis was used to confirm the formation of the complex and several parameters were optimized to obtain a high quality formulation. The water-solubility, drug loading, particle size, zeta potential, morphology and in vivo properties of the SLB-PC-BS-MMs were determined.

Results: The solubility of SLB in water was increased from 40.83 ± 1.18 μg/mL to 10.14 ± 0.36 mg/mL with a high drug loading (DL) of 14.43% ± 0.44% under optimized conditions. The SLB-PC-BS-MMs were observed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) and showed spherical shapes. The particle size and zeta potential, as measured by photon correlation spectroscopy (PCS), were about 30 ± 4.8 nm and -39 ± 5.0 mV, respectively. In vivo studies showed that incorporation of the SLB-PC complex into PC-BS-MMs led to a prolonged circulation time of the drug.

Conclusion: This novel formulation appears to be a good candidate for drug substances that exhibit poor solubility for parenteral administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / administration & dosage*
  • Antioxidants / pharmacokinetics
  • Bile Acids and Salts / chemistry*
  • Calorimetry, Differential Scanning
  • Infusions, Intravenous
  • Micelles*
  • Milk Thistle / chemistry
  • Particle Size
  • Phosphatidylcholines / chemistry*
  • Rats
  • Silybin
  • Silymarin / administration & dosage*
  • Silymarin / pharmacokinetics
  • Solubility

Substances

  • Antioxidants
  • Bile Acids and Salts
  • Micelles
  • Phosphatidylcholines
  • Silymarin
  • Silybin