TY - JOUR
T1 - Use of pure t-butanol as a solvent for freeze-drying
T2 - A case study
AU - Ni, Nina
AU - Tesconi, Marc
AU - Tabibi, S. Esmail
AU - Gupta, Shanker
AU - Yalkowsky, Samuel H.
N1 - Funding Information:
This work was performed under contract CM-77 109 from the National Cancer Institute.
PY - 2001/9/11
Y1 - 2001/9/11
N2 - 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.
AB - 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.
KW - 1-(2-Chloroethyl)-3-sarcosinamide-1-nitrosourea
KW - Lyophilization
KW - Tertiary butyl alcohol
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U2 - 10.1016/S0378-5173(01)00757-8
DO - 10.1016/S0378-5173(01)00757-8
M3 - Article
C2 - 11532568
AN - SCOPUS:0035845724
SN - 0378-5173
VL - 226
SP - 39
EP - 46
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
IS - 1-2
ER -