title: Use of pure t-butanol as a solvent for freeze-drying: a case study.
abstract: 1-(2-Chloroethyl)-3-sarcosinamide-1-nitrosourea, (SarCNU) (NSC-364432) is a new antitumor drug that is of interest to the National Cancer Institute. It is intended for use as an intravenous injection. Although SarCNU is sufficiently soluble in water to obtain the desired dosage, it is highly unstable. 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 melting solvent, was determined to be an excellent freeze-drying medium. Lyophilization of SarCNU from pure TBA produces a uniform cake composed of needle-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% propylene glycol and 10% ethanol. The reconstituted solutions are stable for 4 and 13 h, respectively.
authors.affiliation: College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA. na@pharmacy.arizona.edu
authors.forename: N
authors.initials: N
authors.lastname: Ni
authors.forename: M
authors.initials: M
authors.lastname: Tesconi
authors.forename: S E
authors.initials: SE
authors.lastname: Tabibi
authors.forename: S
authors.initials: S
authors.lastname: Gupta
authors.forename: S H
authors.initials: SH
authors.lastname: Yalkowsky
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002330:Carmustine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005612:Freeze Drying / Q000379:methods*; D007275:Injections, Intravenous; D012997:Solvents; D013678:Technology, Pharmaceutical; D020002:tert-Butyl Alcohol
chemical_list: D000970:Antineoplastic Agents; D012997:Solvents; C044565:2-((((2-chloroethyl)nitrosoamino)carbonyl)amino)propanamide; D020002:tert-Butyl Alcohol; D002330:Carmustine