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

Area of Science:

• Pharmaceutical Compounding
• Drug Stability Studies
• Pediatric Formulations

Background:

• Beyond-use dates (BUDs) are crucial in pharmaceutical compounding, typically derived from stability studies.
• The United States Pharmacopoeia (USP) provides guidelines for BUD assignment, suggesting six months for dry oral dosage forms.
• A new pediatric amiodarone capsule formulation, available in 5 mg, 20 mg, and 50 mg strengths, necessitated specific stability evaluations.

Purpose of the Study:

• To determine the appropriate beyond-use dates (BUDs) for new pediatric amiodarone capsule formulations through comprehensive stability studies.
• To evaluate the impact of different excipients on the stability of amiodarone hydrochloride in capsule preparations.
• To identify potential drug-excipient interactions affecting amiodarone stability.

Main Methods:

• Validated a stability-indicating method for accurate amiodarone content determination.
• Conducted a detailed stability study on amiodarone capsules with varying excipients.
• Compared the stability of amiodarone hydrochloride when formulated with common compounding excipients like microcrystalline cellulose, lactose, and mannitol.

Main Results:

• Amiodarone hydrochloride capsules formulated with microcrystalline cellulose demonstrated dose-dependent stability: 50 mg capsules were stable for 1 year, while 5 mg and 20 mg capsules were not.
• Lactose or mannitol emerged as more suitable excipients for the 5 mg amiodarone capsules, despite potential side effects.
• A specific drug-excipient interaction was identified between amiodarone hydrochloride and microcrystalline cellulose.

Conclusions:

• Capsules of amiodarone hydrochloride compounded with microcrystalline cellulose have assigned beyond-use dates (BUDs) of 1 month for 5 mg, 6 months for 20 mg, and 1 year for 50 mg.
• The choice of excipient is critical for achieving desired BUDs in amiodarone pediatric formulations.
• Further investigation into excipient interactions is warranted for optimizing pediatric compounded medications.