A high-throughput combinatorial approach for the discovery of a cremophor EL-free paclitaxel formulation

Pharm Res. 2003 Aug;20(8):1302-8. doi: 10.1023/a:1025021603288.


Purpose: The purpose of this work was to replace Cremophor-EL in the commercial paclitaxel intravenous formulation, Taxol, using a novel high-throughput combinatorial formulation approach.

Methods: Full factorial combinations of 12 generally regarded as safe excipients at three different concentrations were screened using an automated liquid dispenser. The hit formulations were further optimized to give the final optimized formulation TPI-1. TPI-1 was then tested in rats to compare its pharmacokinetic profile to Taxol.

Results: Of the 9,880 combinations tested in the initial screen, 19 were identified as hit combinations. These were further optimized to give the final formulation TPI-1. When tested in rats, TPI-1 was well tolerated at both the low and high doses of 5 mg/kg and 10 mg/kg, whereas Taxol killed all the rats at the high dose. TPI-1 experienced slower elimination compared to Taxol. Similar to Taxol, TPI-1 also exhibited nonlinear pharmacokinetics.

Conclusions: This study demonstrated the power of a high-throughput combinatorial approach for alternative paclitaxel formulations. We believe that this approach can be applied to drug formulation in general and it can improve the speed and efficiency of drug formulation design.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Chemistry, Pharmaceutical
  • Combinatorial Chemistry Techniques*
  • Dose-Response Relationship, Drug
  • Drug Compounding*
  • Excipients / chemistry*
  • Glycerol / analogs & derivatives*
  • Glycerol / chemistry
  • Male
  • Paclitaxel / administration & dosage
  • Paclitaxel / chemistry*
  • Paclitaxel / pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors


  • Excipients
  • cremophor EL
  • Paclitaxel
  • Glycerol