Drug Design, Development and Therapy (Jun 2021)
Stability of Aprepitant Injectable Emulsion in Alternate Infusion Bags, in Refrigerated Storage, and Admixed with Dexamethasone and Palonosetron
Abstract
Thomas Ottoboni, 1 Laura Lerner, 1 Arlene Santhouse 2 1Pharmaceutical and Translational Science, Heron Therapeutics, Inc, San Diego, CA, USA; 2Medical Affairs, Heron Therapeutics, Inc, San Diego, CA, USACorrespondence: Thomas OttoboniPharmaceutical and Translational Science, Heron Therapeutics, Inc, 4242 Campus Point Court, Suite 200, San Diego, CA, 92121, USATel +1 650-261-3003Fax +1 650-365-6490Email [email protected]: The stability of aprepitant injectable emulsion is evaluated in various admixture bags and solutions, under different storage conditions, and when combined with other antiemetics.Methods: A volume of 18 mL aprepitant injectable emulsion was added to infusion bags (either non-di-(2-ethylhexyl) phthalate [DEHP], polyvinyl chloride [PVC]-containing bags or non-DEHP, non-PVC bags) containing 100, 130, or 250 mL of 0.9% normal saline solution (NSS) or 5% dextrose in water (D5W). Bags were stored at controlled room temperature (20– 25°C) for up to 12 hours or refrigerated (2– 8°C) for up to 72 hours. Compatibility/stability was also assessed in admixtures combined with either dexamethasone or palonosetron. At specified time points, bags were tested for appearance, pH, assay for aprepitant (ie, percent label claim of aprepitant) and aprepitant-related substances, Z-average particle size, globule size distribution, particulate matter, and DEHP content (PVC bags). In separate analyses to assess microbial burden, bags containing aprepitant were inoculated with seven different organisms and assessed for microbial growth.Results: There was no detectable impact on the physicochemical properties or potential to promote microbial growth of aprepitant when diluted with various amounts of either NSS or D5W and when admixed with either dexamethasone or palonosetron at room temperature for at least 6 hours or during refrigeration for up to 72 hours in either PVC- or non-PVC-containing bags.Conclusion: Aprepitant-containing admixtures are stable under these conditions, a finding that may improve patient and provider convenience and reduce medication wastage.Keywords: chemotherapy-induced nausea and vomiting, di-(2-ethylhexyl) phthalate, DEHP, microbial growth, physicochemical, polyvinyl chloride, PVC
