Stability of Docetaxel Solution: METHODS part 2

Stability Study

On study day 0, 10 vials of the new formulation of the commercially available docetaxel product (Taxotere, Aventis Pharma Inc, lot 3P732, expiry October 2005) were diluted with the supplied diluent (13% ethanol in water, lot 2H748, expiry December 2003) according to the manufacturer’s instructions. Three of these vials were stored at room temperature (23°C) and 3 were stored in the refrigerator (4°C); the docetaxel concentration was determined in duplicate on study days 0, 1, 3, 4, 7, 10, 14, 17, and 21. The remaining 4 vials were further diluted in NS to prepare nominal concentrations of 0.4 and 0.8 mg/mL (equivalent to 20 and 40 mg per 50 mL) which were stored in PABs (B Braun Medical Inc, Irvine, California, lot J2D954, expiry July 2003). An additional sample of the older formulation (Taxotere, Rhone-Poulenc Rorer, Ville Saint-Laurent, Quebec, lot 1A154 for docetaxel solution and lot 1C429 for diluent; expiry June 2002) was also prepared according to the manufacturer’s instructions and was then further diluted in NS to prepare a nominal concentration of 0.8 mg/mL (equivalent to 80 mg per 100 mL) in a PAB. All PABs were stored at room temperature, unprotected from ambient fluorescent room light during the study. On study days 0, 3, 7, 14, 25, and 35, the concentration of docetaxel was determined in duplicate.

Visual Inspection and pH

Visual inspection was carried out as samples were drawn for pH analysis on day 0 and day 35. The samples were drawn, placed in a 10 x 75 mm glass test tube and inspected visually for colour and clarity against a black background and a white background. The pH of each solution was then measured and recorded to the nearest 0.001 of a pH unit. The pH meter (Accumet model 925, Fisher Scientific, Toronto, Ontario) was equipped with a microprobe glass body electrode (cat­alogue no. 13-639-280, Fisher Scientific, Toronto, Ontario). To ensure the accuracy of the pH measure­ments, the pH meter was standardized on day 0 and day 35 with commercially available buffer solutions (pH 7.00 and 4.00; Fisher Scientific, Nepean, Ontario).
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Data Reduction and Statistical Analysis

Means were calculated for analyses completed in duplicate. Error was assessed by CV. Mean concentrations (or percent remaining) for different days were compared statistically by least-squares multiple linear regression, using concentration, formulation, temperature, and study day as sources of error in the analysis of variance (ANOVA) model to determine if there was an association between concentration and time. The 5% level was used as the a priori cut-off for significance, and all references to significance refer to this level. The lower limit of the 95% confidence interval of concentra­tions determined by linear regression was determined. Docetaxel concentrations were considered acceptable or within acceptable limits if the lower limit of the 95% confidence interval of the mean concentration remaining was greater than 90% of the initial (day 0) concentration.

Category: Main

Tags: docetaxel, stability, Taxotere

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