Stability Studies of Ternary Mixtures Containing Fosaprepitant,Dexamethasone, Ondansetron and Granisetron Used in Clinical Practice

Abstract

The use of a combination of 5HT3 receptor antagonist, a NK-1 receptor antagonist and dexamethasone has been classified to be state of the art in patients receiving highly as well as moderately emetogenic chemotherapy like cisplatin and anthracyclines. The administration of the ad-hoc admixture of fosaprepitant, dexamethasone and ondansetron (FDO) or granisetron (FDG) in the same IV infusion solution will improve the management of ambulatory procedures related to reducing administration time and number of administered intravenous preparations. All this would improve patient safety and comfort. In order to guarantee security of patients and efficacy of treatment, information about physico-chemical stability of both ternary mixtures at concentrations used in routine clinical practice and at different conditions of storage is needed. In this study, physico-chemical stability of ternary mixtures of fosaprepitant (150 mg), dexamethasone (8 mg) and ondansetron (8 mg) or granisetron (3 mg) in 50,100 and 250 ml of 0.9 g/dl NaCl at room temperature/refrigerated and protective from/exposed to light has been evaluated. An HPLC method has been developed and validated according to International Conference on Harmonization guidelines to evaluate chemical stability of drugs in mixtures simultaneously. Physical stability study has been carried out by visual inspection, pH measure and gravimetry to control evaporation. The results shown in this paper represent the first evidence of the physico-chemical stability of both ternary mixtures used in clinical practice at different conditions of storage. The ternary mixtures of FDG in 100 and 250 ml of 0.9 g/dl NaCl are physico-chemical stable for 15 days at room temperature and refrigerated and exposed to and protected from light; mixtures in 50 ml are physico-chemical stable for 6 days. The ternary mixtures of FDO in 50, 100 and 250 ml of 0.9 g/dl NaCl are physico-chemical stable for 15 days at both conditions of temperature and light.