Pharmaceutical Development of a Parenteral Formulation of the Investigational Anticancer Drug Clanfenur

Jantine D. Jonkman-De Vries; Bart J. F. Van Den Bemt; Wim W. Ten Bokkel-Huinink; Willy J. M. Underberg; J. Jantina Kettenes-Van Den Bosch; Roland E. C. Henrar; Auke Bult; Jos H. Beijnen

Abstract

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°C and of 4 months at 25°C is calculated.

Received February 5, 1996.
Accepted November 4, 1996.

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