title: Compatibility and Stability of Rolapitant Injectable Emulsion Admixed with Intravenous Palonosetron Hydrochloride.
abstract: Neurokinin-1 receptor antagonist, 5-hydroxytryptamine-3 RA, and dexamethasone combination therapy is standard of care for the prevention of chemotherapy-induced nausea and vomiting. Herein we describe the physical and chemical stability of rolapitant injectable emulsion 166.5 mg in 92.5 mL (185 mg hydrochloride salt) admixed with palonosetron injection 0.25 mg in 5 mL (0.28 mg hydrochloride salt). Admixtures were prepared and stored in two types of container closures (110-mL Crystal Zenith plastic and glass bottles) and four types of intravenous administration sets (or intravenous tubing sets). Assessment of the physical and chemical stability was conducted on the admixtures in the ready-to-use container closure systems as supplied by the manufacturer, stored at room temperature (20°C to 25°C under fluorescent light), and evaluated at 0, 1, and 6 hours; 1 and 2 days; and under refrigeration (2°C to 8°C protected from light) after 1, 3, and 7 days. 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 initially, and then after 20 hours (total 27 hours) at 2°C to 8°C protected from light. Physical stability was assessed by visual examination of the container 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 and impurity levels with high-performance liquid chromatographic analysis. The results indicated that all samples were physically compatible throughout the duration of the study. The pH, turbidity, and particulate matter of the admixture stayed within narrow and acceptable ranges. Rolapitant admixed with palonosetron was chemically stable when admixed in glass and Crystal Zenith bottles for at least 48 hours at room temperature and for 7 days under refrigeration, as well as in the four selected intravenous tubing sets for 7 hours at 20°C to 25°C and then for 20 hours at 2°C to 8°C. No loss of potency of any admixed components occurred in the samples stored at the two temperature ranges and time period 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; D004338:Drug Combinations; D004344:Drug Incompatibility; D004349:Drug Packaging; D004355:Drug Stability; D004356:Drug Storage; D004655:Emulsions; D005898:Glass / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D007546:Isoquinolines / Q000008:administration & dosage / Q000737:chemistry*; D008027:Light; D064729:Neurokinin-1 Receptor Antagonists / Q000008:administration & dosage / Q000737:chemistry*; D000077924:Palonosetron; D010969:Plastics / Q000737:chemistry; D011812:Quinuclidines / Q000008:administration & dosage / Q000737:chemistry*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D013141:Spiro Compounds / Q000008:administration & dosage / Q000737:chemistry*; D013696:Temperature; D013997:Time Factors
chemical_list: D000932:Antiemetics; D004338:Drug Combinations; D004655:Emulsions; D007546:Isoquinolines; D064729:Neurokinin-1 Receptor Antagonists; D010969:Plastics; D011812:Quinuclidines; D012702:Serotonin Antagonists; D013141:Spiro Compounds; D000077924:Palonosetron; C578834:rolapitant