Pharmaceutical development of a parenteral formulation of the investigational anticancer drug clanfenur.
A stable parenteral dosage form for the investigational cytotoxic drug clanfenur was designed, and the bulk drug was characterized by its nuclear magnetic resonance, mass spectrometry, infrared, and ultraviolet spectra. The 1H and 13C spectra show clanfenur to be a mixture of two stereoisomers. Because of poor solubility in aqueous solution and precipitation in co-solvent, surfactant, or emulsion systems, a two-pump infusion system was developed for intravenous administration. Clanfenur, solubilized in a Cremophor EL/ethanol (1:1, w/v) solution (concentration, 15 mg/mL), can be simultaneously infused with 5% dextrose infusion fluid. Total doses of up to 1,680 mg of clanfenur (and 56 g of Cremophor EL) theoretically can be administered to patients over a 6-hour period. From accelerated stability testing of clanfenur in the Cremophor EL/ethanol (1:1, w/v) formulation, a shelf life of 3.5 years at 4 degrees C and of 4 months at 25 degrees C is calculated.
Jonkman-de Vries
J D
JD
Department of Pharmacy, Slotervaart Hospital/Netherlands Cancer Institute, Amsterdam, The Netherlands.
Van den Bemt
B J
BJ
ten Bokkel-Huinink
W W
WW
Underberg
W J
WJ
Kettenes-van den Bosch
J J
JJ
Henrar
R E
RE
Bult
A
A
Beijnen
J H
JH
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000032:analysis* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004132:Diflubenzuron / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry; D004304:Dosage Forms; D004355:Drug Stability; D015507:Drugs, Investigational / Q000008:administration & dosage* / Q000032:analysis / Q000737:chemistry; D007262:Infusions, Intravenous; D007263:Infusions, Parenteral; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D012995:Solubility; D012996:Solutions / Q000737:chemistry; D013053:Spectrophotometry; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D004304:Dosage Forms; D015507:Drugs, Investigational; D012996:Solutions; D004132:Diflubenzuron; C086806:clanfenur