title: Compatibility and Stability of Rolapitant Injectable Emulsion Admixed with Dexamethasone Sodium Phosphate.
abstract: Neurokinin-1 receptor antagonist, 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone combination therapy is the standard of care for the prevention of chemotherapy-induced nausea and vomiting. Herein, we describe the physical and chemical stability of an injectable emulsion of the Neurokinin-1 receptor antagonist rolapitant 185 mg in 92.5 mL (free base, 166.5 mg in 92.5 mL) admixed with either 2.5 mL of dexamethasone sodium phosphate (10 mg) or 5 mL of dexamethasone sodium phosphate (20 mg). Admixtures were prepared and stored in two types of container closures (glass and Crystal Zenith plastic bottles) and four types of intravenous administration tubing sets (or intravenous tubing sets). The assessment of the physical and chemical stability was conducted on admixtures packaged in bottled samples stored at room temperature (20°C to 25°C under fluorescent light) and evaluated at 0, 1, and 6 hours. For admixtures in intravenous tubing sets, the assessment of physicochemical stability was performed after 0 and 7 hours of storage at 20°C to 25°C, and then after 20 hours (total 27 hours) under refrigeration (2°C to 8°C) and protected from light. Physical stability was assessed by visually examining the bottle contents under normal room light and measuring turbidity and particulate matter. Chemical stability was assessed by measuring the pH of the admixture and determining drug concentrations through high-performance liquid chromatographic analysis. Results showed that all samples were physically compatible throughout the duration of the study. The admixtures stayed within narrow and acceptable ranges in pH, turbidity, and particulate matter. Admixtures of rolapitant and dexamethasone were chemically stable when stored in glass and Crystal Zenith bottles for at least 6 hours at room temperature, as well as in the four selected intravenous tubing sets for 7 hours at 20°C to 25°C and then for 20 (total 27 hours) hours at 2°C to 8°C. No loss of potency of any admixed component occurred in the samples stored at the temperature ranges studied.
authors.affiliation: TESARO Inc., Waltham, Massachusetts. gwu@tesarobio.com.
authors.forename: George
authors.initials: G
authors.lastname: Wu
authors.affiliation: TESARO Inc., Waltham, Massachusetts.
authors.forename: Stanley
authors.initials: S
authors.lastname: Yeung
authors.affiliation: TESARO Inc., Waltham, Massachusetts.
authors.forename: Frank
authors.initials: F
authors.lastname: Chen
mesh_terms: D000932:Antiemetics / Q000008:administration & dosage / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D004338:Drug Combinations; D004339:Drug Compounding; D004344:Drug Incompatibility; D004349:Drug Packaging; D004355:Drug Stability; D004356:Drug Storage; D004655:Emulsions; D005898:Glass / Q000737:chemistry; D005938:Glucocorticoids / Q000008:administration & dosage / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D008027:Light; D064729:Neurokinin-1 Receptor Antagonists / Q000008:administration & dosage / Q000737:chemistry*; D010969:Plastics / Q000737:chemistry; D013141:Spiro Compounds / Q000008:administration & dosage / Q000737:chemistry*; D013696:Temperature; D013997:Time Factors
chemical_list: D000932:Antiemetics; D004338:Drug Combinations; D004655:Emulsions; D005938:Glucocorticoids; D064729:Neurokinin-1 Receptor Antagonists; D010969:Plastics; D013141:Spiro Compounds; C004180:dexamethasone 21-phosphate; D003907:Dexamethasone; C578834:rolapitant