Patenteral 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 β-cydodextrin/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.