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

Nina Ni, Marc Tesconi, S. Esmail Tabibi, Shanker Gupta, Samuel H Yalkowsky

Research output: Contribution to journalArticle

41 Scopus citations

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 T90 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.

Original languageEnglish (US)
Pages (from-to)39-46
Number of pages8
JournalInternational Journal of Pharmaceutics
Volume226
Issue number1-2
DOIs
Publication statusPublished - Sep 11 2001

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Keywords

  • 1-(2-Chloroethyl)-3-sarcosinamide-1-nitrosourea
  • Lyophilization
  • Tertiary butyl alcohol

ASJC Scopus subject areas

  • Pharmaceutical Science

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