Parenteral formulation of Flavopiridol (NSC-649890).
Flavopiridol [5,7-dihydroxy-8-(4-N-methyl-2-hydroxypyridyl)-6' -chloroflavone hydrochloride] is a flavonoid with weak electrolyte properties and an intrinsic aqueous solubility of 0.024 mg/mL. Neither cosolvency complexation, nor pH control alone can produce an acceptable 10 mg/mL formulation that will not precipitate when diluted with blood. However, a combination of buffer and cyclodextrin or buffer and cosolvent can produce an acceptable 10 mg/mL formulation. In this paper, Flavopiridol is shown to be stable for at least one year in 30% hydroxypropyl beta-cyclodextrin/0.1 M citrate buffer (4.52). This formulation does not precipitate for at least one hour upon dilution with Sorensen's phosphate buffer pH 7.4.
Dannenfelser
R M
RM
University of Arizona, College of Pharmacy, Tucson, Arizona, USA.
Surakitbanharn
Y
Y
Tabibi
S E
SE
Yalkowsky
S H
SH
D002021:Buffers; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005419:Flavonoids / Q000737:chemistry*; D006131:Growth Inhibitors / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007262:Infusions, Intravenous; D010880:Piperidines / Q000737:chemistry*; D012995:Solubility
D002021:Buffers; D005419:Flavonoids; D006131:Growth Inhibitors; D010880:Piperidines; C077990:alvocidib