16 Beyond Use Date and Stability of Compounded Preparations

Beyond Use Date

When pharmaceutical preparations are compounded, we must determine how long the product is good for.

The Beyond-Use Date (BUD) is the date after which a non-sterile compounded preparation should no longer be used. Unlike expiry dates assigned to manufactured drug products, BUDs for non-sterile compounded preparations are determined based on different criteria due to the immediate-use or short-term storage nature of these preparations. Assigning a BUD is different from using a manufacturer’s expiry date and must be based on a careful evaluation of the formulation’s stability, the compounding process, and storage conditions.  Assigning a BUD requires extensive experience in non-sterile compounding, as well as a strong understanding of stability data and formulation properties.

If you have an existing Master Formulation Record with an established BUD, you simply need to calculate the date, using the day the compound is made as Day 1. If you have to create a Master Formulation record from scratch, you need to calculate and determine the Beyond Use Date.

Considerations for Assigning a BUD

BUDs should be assigned conservatively, considering factors such as:

• The stability of the active pharmaceutical ingredient (API) and excipients
• Information provided by the manufacturer (if using a commercial product as an API)
• The compounding method and formulation type
• Potential degradation mechanisms
• Compatibility of ingredients
• Potential for microbial growth within the preparation
• The type of container used for storage
• Expected storage conditions (e.g., refrigeration or room temperature)
• The intended use and duration of therapy

Consult references and assign according to published monograph or formulation record (USP, Trissel’s, Remington’s, Sickkids).  The manufacturer’s expiry date of an API should not be used as the BUD for the final compounded preparation. Instead, appropriate references and stability data should be reviewed.  If not known, use the “default” dates for nonsterile preparations according to NAPRA.

NAPRA Default Beyond-Use Date (BUD) Guidelines (When No Stability Data Exists)

• Non-aqueous formulations (e.g., capsules, ointments without water):
  Assign a BUD not later than the earliest expiry date of any ingredient or 6 months, whichever is earlier.
• Water-containing oral formulations (e.g., oral suspensions, solutions):
  Assign a BUD not later than 14 days, with refrigeration required at controlled cold temperatures.
• Water-containing topical/dermal, mucosal liquid, and semi-solid formulations (e.g., creams, gels):
  Assign a BUD not later than 30 days.

*Recommended BUDs in absence of stability information

*Never assign a BUD longer than the expiry date of any component

Stability of Compounded Preparations

Stability refers to the ability of a compounded preparation to maintain its physical, chemical, microbiological, therapeutic, and toxicological properties throughout its assigned Beyond-Use Date (BUD). A stable product ensures that the patient receives the expected dose, efficacy, and safety profile throughout the entire period of use.

• Type of preparation: Liquid, semi-solid, or solid formulations behave differently.

• pH and solubility: Extreme pH or poor solubility may lead to precipitation or degradation.

• Storage conditions: Heat, light, and moisture can break down APIs or excipients.

• Packaging: Light-resistant or airtight containers may be necessary.

• Presence of water: Water supports microbial growth and may shorten stability.

• Compatibility of ingredients: Some ingredients degrade each other when mixed

Additional Stability Considerations

• Microbial Growth Prevention – Where applicable, antimicrobial agents should be included to prevent bacterial, yeast, and mold contamination. However, these agents should not replace proper compounding practices.
• Storage Requirements – If antimicrobial preservatives are contraindicated, susceptible compounded products should be stored at controlled cold temperatures, and patients should be informed of proper storage practices. *Always label for proper storage.
• Monitoring for Instability – The compounded preparation should be examined at all stages for signs of instability or degradation, including changes in color, consistency, separation, gas production or odor.
• Ensure patient counseling on storage after dispensing.
• Document any known stability data used to support BUD assignment.

Assigning a BUD is more than a technical requirement—it’s a critical safety decision based on your understanding of stability principles. A compounded preparation must remain stable and effective throughout its assigned BUD, and that means pharmacy personnel must be familiar with factors like pH, ingredient compatibility, storage conditions, and microbial risk. By using reputable references and observing best practices, pharmacy personnel help ensure that patients receive safe, high-quality compounds. Remember: when in doubt, consult stability resources or default to conservative guidelines. A cautious, science-informed approach is always the safest path in compounding.