Pharmaceutical development of a parenteral lyophilized formulation of the novel indoloquinone antitumor agent EO9

Cancer Chemother Pharmacol. 1994;34(5):416-22. doi: 10.1007/BF00685567.

Abstract

The aim of this study was to design a stable parenteral dosing form of the investigational cytotoxic drug, encoded EO9. EO9 exhibits poor aqueous solubility and stability characteristics. Freeze-drying was selected as the manufacturing process. Differential scanning calorimetry studies were conducted to determine the freeze-drying cycle parameters. A stable lyophilized formulation of EO9 was developed. The prototype, containing 8.0 mg EO9 and 200 mg lactose/vial, was found to be the optimal formulation in terms of solubility, length of the freeze-drying cycle, stability, and dosing requirements for phase I clinical trials. Quality control of the freeze-dried formulation showed that the manufacturing process does not change the integrity of EO9. Shelf-life studies demonstrated that the formulation remains stable for at least 1 year when stored at +4 degrees C in a dark environment.

Publication types

  • Comparative Study

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Aziridines / chemistry*
  • Calorimetry, Differential Scanning
  • Chromatography, High Pressure Liquid
  • Drug Stability
  • Drug Storage
  • Freeze Drying / methods*
  • Indolequinones*
  • Indoles / chemistry*
  • Quality Control
  • Quinones / chemistry
  • Solubility
  • Spectrophotometry, Ultraviolet
  • Technology, Pharmaceutical*

Substances

  • Antineoplastic Agents
  • Aziridines
  • Indolequinones
  • Indoles
  • Quinones
  • EO 5A
  • apaziquone