Beyond-Use Dates Assignment for Pharmaceutical Preparations: Example of Low-Dose Amiodarone Capsules

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.

Paediatric capsule compounding in hospital practices: by weight or by volume?

“…In addition, as ‘hospital preparations’ (preparations made in batches for several patients) must be as reproducible as possible, the weight-based method should be preferred for their compounding. The API/excipient ratio may influence the stability of the capsule13 and consequently the beyond-use date (BUD). Batch reproducibility thus improves BUD reproducibility 14.…”

Low-dose erythromycin in pediatrics: Formulation and stability of 20 mg hard gelatin capsules

“…Disintegration tests were performed on 6 capsules at time zero, one month, 3 months, 8 months, and 12 months. Significant changes in erythromycin content were defined as a 10% change in dosage from its initial value as previously reported for hospital-compounded preparations [29][30][31][32][33].…”