What Factors Influence Stability?

Stability measures the extent to which a product retains, within specified limits, and throughout its period of storage and use, the same properties and characteristics it possessed at the time of compounding. According to USP <1191>, pharmacists should establish and maintain compounding conditions that ensure drug stability to help prevent therapeutic failure and adverse responses.

There are five stability considerations:

Type of Stability
Conditions Maintained Throughout the Shelf Life of the Drug Product
Each active ingredient retains its chemical integrity and labeled potency, within the specified limits.
The original physical properties, including appearance, palatability, uniformity, dissolution, and suspendability, are retained.
Sterility or resistance to microbial growth is retained according to the specified requirements. Antimicrobial agents that are present retain effectiveness within the specified limits.
The therapeutic effect remains unchanged.
No significant increase in toxicity occurs.

According to USP <795>, at all steps in the compounding, dispensing, and storage process, the compounder shall observe the compounded drug preparation for signs of instability. Each ingredient in a formulation can affect the stability of drug products and dosage forms. Environmental factors that reduce stability include adverse temperatures, light, humidity, oxygen, and carbon dioxide. Dosage form factors that reduce stability and cause active drug content loss include particle size (especially in emulsions and suspensions), pH, solvent system composition, compatibility of anions and cations, solution ionic strength, primary container, specific chemical additives, and molecular binding and diffusion of drugs and excipients.
All stability characteristics should be considered when assigning a beyond use date (BUD) for a preparation. A BUD is the date after which a compounded preparation shall not be used and is determined from the date the preparation is compounded. USP <797> allows for the use of the literature for BUD assignment but speaks to the risks of doing so. The most accurate way to assign a BUD is to perform testing over time to demonstrate the product maintains chemical, physical, and microbiological properties. A stability study commonly includes: a stability indicating method assay, sterility (for sterile preparations), endotoxin (for most sterile preparations), pH, visual inspection, particulate matter, preservative effectiveness and preservative quantification (for preserved preparations), microbial limits (for non-sterile preparations), and the absence of specified organisms (for non-sterile preparations). 
In the absence of stability or sterility information, USP <795> and <797> provide guidance for maximum BUD recommendations. A stability study is required to extend the dating of a product that exceeds the maximum USP BUD recommendations. It is important pharmacists ensure their drug products meet acceptable stability criteria and avoid ingredients or conditions that could cause physical deterioration or chemical decomposition.

For more information on stability testing, contact ARL at 800-393-1595 or info@arlok.com


USP <795> Pharmaceutical Compounding—Nonsterile Preparations

USP <797> Pharmaceutical Compounding—Sterile Preparations

USP <1191> Stability Considerations in Dispensing Practice