Pharmaceutical development of a parenteral lyophilized formulation of the novel indoloquinone antitumor agent EO9.
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.
Jonkman-de Vries
J D
JD
Department of Pharmacy, Slotervaart Hospital/Netherlands Cancer Institute, Amsterdam.
Talsma
H
H
Henrar
R E
RE
Kettenes-van den Bosch
J J
JJ
Bult
A
A
Beijnen
J H
JH
D000970:Antineoplastic Agents / Q000737:chemistry*; D001388:Aziridines / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D004356:Drug Storage; D005612:Freeze Drying / Q000379:methods*; D045563:Indolequinones; D007211:Indoles / Q000737:chemistry*; D011786:Quality Control; D011809:Quinones / Q000737:chemistry; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013678:Technology, Pharmaceutical
D000970:Antineoplastic Agents; D001388:Aziridines; D045563:Indolequinones; D007211:Indoles; D011809:Quinones; C082259:EO 5A; C060817:apaziquone