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Abstract:  Conventional paclitaxel admixtures are not physically stable; precipitation occurs which interferes with multiday continuous infusion, a delivery mode being evaluated in clinical trials. The purpose of this article is to describe an extemporaneous compounding approach that extends the stability of paclitaxel admixtures and to provide documentation of the pharmaceutical acceptability of these admixtures.

Paclitaxel admixtures have been found to be chemically stable until they precipitate. Microcrystalline precipitation may begin after 3 days. The physical stability of paclitaxel admixtures was found to increase when ethanol concentrations in the final admixtures were raised from the usual 8.3% to 20% to 25% or more.

The extended-stability admixtures were compounded at a paclitaxel concentration of 1 mg/mL by adding additional sterile dehydrated alcohol injection, USP, along with the paclitaxel concentrate for injection to 5% dextrose injection, USP, to bring the ethanol concentration to 20% and to 25% in the final admixtures. The chemical and physical stability of the admixtures was evaluated at 4°, 22°, and 32° C over periods up to 31 days. Using a stability-indicating high-performance liquid chromatographic assay, no loss of paclitaxel due to decomposition was found in any sample. Precipitation occurred in a few samples within the observation periods. Substantial losses (up to 70%) occurred in the few samples that precipitated.

The addition of sterile dehydrated alcohol injection, USP, to paclitaxel admixtures in 5% dextrose injection, increasing the final ethanol concentration to about 25%, results in paclitaxel admixtures that are physically and chemically stable for at least 7 days, and possibly up to 14 days, at 4°, 22°, and 32° C.

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