Use of pure t-butanol as a solvent for freeze-drying: a case study

1-(2-Chloroethyl)-3-sarcosinamide-1-nitrosourea, (SarCNU) (NSC-364432) is a new antitumor drug that is of interest to the National Cancer Institute. I t is intended for use as an intravenous injection. Although SarCNU is suffi ciently soluble in water to obtain the desired dosage, it is highly unstabl e. Its T-90 in aqueous solution at room temperature is less than 6 h. Neat tertiary butyl alcohol (TBA), a low toxicity, high vapor pressure and low m elting solvent, was determined to be an excellent freeze-drying medium. Lyo philization of SarCNU from pure TBA produces a uniform cake composed of nee dle-shaped crystals. Thermal analysis and gas chromatography indicate that the cake contains less than 0.001% residual solvent. The SarCNU cake can be readily reconstituted with either water or an aqueous solution of 40% prop ylene glycol and 10% ethanol. The reconstituted solutions are stable for 4 and 13 h, respectively. (C) 2001 Elsevier Science B.V. All rights reserved.