Beyond-Use Dates Assignment for Pharmaceutical Preparations: Example of Low-Dose Amiodarone Capsules. (August 2021)

• Record Type: Journal Article
• Authors: Brun, Damien; Curti, Christophe; Lamy, Edouard; Jean, Christophe; Bertault-Peres, Pierre; Broggi, Julie; Tintori, Guillaume; Vanelle, Patrice
• Is Part Of: Journal of pharmacy technology. Volume 37:Number 4(2021)
• Page Start: 178
• Page End: 185
• Publication Date: 2021-08
• Subjects: drug compounding -- stability -- drug-excipient interaction -- amiodarone -- microcrystalline cellulose; Pharmacy -- Periodicals; Pharmaceutical technology -- Periodicals; Chemotherapy -- Periodicals; 615.105
• DOI: 10.1177/87551225211015566
• Languages: English
• ISSNs: 8755-1225

Abstract

Background: Beyond-use dates (BUDs) in compounding practice are assigned from stability studies. The United States Pharmacopoeia (USP 42 NF 37) suggested to assign a 6 months BUD for dry oral forms. A new pediatric formula of amiodarone capsules was implemented in our hospital, with 3 dosages (5 mg, 20 mg, and 50 mg).Objective: BUD of these new formulas had to be determined by stability study.Methods: The method for the determination of amiodarone content was validated to be stability indicating, and a stability study was performed. Different excipients commonly used for capsule compounding were compared.Results: We found that, with microcrystalline cellulose as excipient, 50 mg amiodarone capsules were stable for 1 year, whereas 5 mg and 20 mg capsules were not. This difference was studied, and lactose or mannitol were found to be better excipients for 5 mg amiodarone capsules, despite their potential side effects. A potential drug-excipient interaction between microcrystalline cellulose and amiodarone hydrochloride is described.Conclusion: Amiodarone hydrochloride/microcrystalline cellulose capsules have a BUD of 1 month for 5 mg capsules, 6 months for 20 mg, and 1 year for 50 mg.