Factors influencing expiration date Flashcards
What is Expiration date/shelf life?
Period when at least 90% of the drug is available for delivery.
Reconstituted/diluted formulations assigned shorter times.
T/F
True
Remember
Products must have labels that specify:
storage requirements, expiration dates, latest time of day for use (when appropriate)
What can affect Expiration dates?
or
Concentration or bioavailability of the active ingredients in a preparation can be affected by:
Physical
chemical
delivery system-related incompatibility / instability / sterility considerations
What does Shelf life refer to?
remember it is determined based on rigorous testing.
assigned to a commercially manufactured intact drug product
Reflects the longest time during which the product will meet the requirements of the USP compendial monograph, under the stated storage conditions.
90% or more of the labeled active ingredient is available
Period when drug or container degradation by products remain below compendial maximum levels.
When determining expiration dates you should…
Should be in accordance with approved product approved labeling
Consult with the manufacturer if deviating from package insert
What is Beyond use dating (BUD)?
Remember this date is assigned based on two factors :stability and sterility
Product is reconstituted, diluted, and transferred into another container or administration device
Date or time after which:
a compounded product should not be used
CSP should not be stored or transported from the date or time, the preparation is compounded
Reflects the potential for microbial, physical, or chemical contamination during compounding
What does stability refer to?
- Active ingredient chemical stability
Maximum time in which 90% or greater of a labeled active ingredient is measurable in the solution and container specified, under the stated storage and administration conditions. - Sterility limitation for the risk level
What does incompatibility refer to?
Physical or chemical phenomenon that reduces the concentration of the active ingredient(s)
These Physicochemical phenomena include:
1. Concentration dependent precipitation
2. Acid-base reactions
What does Physical incompatibility result in?
visible changes, precipitation, cloudiness or haziness, color change, viscosity, effervescence
that May be related to solubility changes or container interactions
What does instability refer to?
Continuous and irreversible chemical reactions
that results in different chemical entity (degradation products)
These products may be therapeutically inactive but still exhibit toxicity (hydrolysis and oxidative reactions)
PHYSICAL INCOMPATIBILITIES
Solubility
Explain why some drugs remain soluble while some precipitate.
How to improve solubility of poorly water soluble drugs?
Explain what occurs when they are diluted with water.
drugs dissolve in water only up to a certain limit (saturation solubility). If the drug concentration stays below this limit, it remains dissolved in the solution. However, if the concentration exceeds this limit (supersaturation), the drug may start forming solid particles (precipitation).
To improve solubility, poorly water-soluble drugs are often mixed with water-miscible solvents like ethanol, propylene glycol, or polyethylene glycol (e.g., diazepam injection).
However, when these formulations are diluted with water, the drug may come out of solution and form solid particles if the concentration exceeds saturation.
If the dilution continues and the concentration falls below the saturation point, the mixture becomes stable again, meaning no more precipitation occurs.
PHYSICAL INCOMPATIBILITIES
pH effect on solubility
Some drugs do not dissolve well in water. To improve their solubility, they are often converted into salts.
Explain how weak acids and bases are converted to salts.
What happens if they are mixed with other salts.
Weak acids are turned into salts by combining them with strong bases (e.g., sodium salt of a weak acid).
Weak bases are turned into salts by combining them with strong acids (e.g., hydrochloride salt of a weak base).
However, when these salts are mixed with other salts (especially salts of weak bases and strong acids), they can cause incompatibilities. This means they might react, form precipitates, or degrade, making the mixture unstable.
PHYSICAL INCOMPATIBILITIES
Stability/solubility may be affected by the pH of the diluting/reconstituting solution
Explain two instances where pH and solvents cause precipitation and breakdown.
The stability and solubility of a drug can change depending on the pH of the solution it is mixed with.
Example: Salts of weak acids and strong bases (like sodium salts) may become less stable in acidic IV solutions (e.g., dextrose 5%, which has a pH of 4.5–5.5). This can cause the drug to precipitate or degrade.
Some drugs are dissolved in non-aqueous solvents (like alcohol or oils) to improve their solubility and stability. However, when these are mixed into a fully aqueous IV solution, the solvent or pH changes may cause the drug to come out of solution (precipitate) or break down chemically
What is sorption?
Sorption refers to the loss of a drug from a solution due to absorption to the surface or into the matrix of the container, administration set or filter
e.g., diazepam, warfarin, insulin, nitroglycerin
Adsorption vs Absorption
Why is adsorption important for small dose/low concentration drugs?
Adsorption
drug sticks to the surface of the container or tubing.
This is important for drugs given in small doses or low concentrations, as clinically relevant amount of drug may be removed from the solution
Absorption
Substance being taken up throughout the entire volume of another material
Drug is absorbed into the matrix of plastic containers and administration sets made of PVCs
This is a major issue for lipid-soluble drugs, as they dissolve into the plastic
Specialized administration sets may be needed
List and explain the other physical incompatibilities.
Salting out
Precipitation of organic drugs in the presence of strong electrolytes
Complexation
Formation of chelates, e.g., tetracycline with aluminum, calcium, iron and magnesium
Color changes
Chemical degradation to a colored decomposition product and gas evolution
Explain and list the types of Chemical degradation.
What increases the rate of degradation in photolysis?
can be Visible (color and gas evolution) or Not visible.
Hydrolysis, Oxidation, Reduction, Photolysis
With photolysis,
The more intense the light source and the closer the drug is to it, the greater the rate of degradation
What are the Types of drug delivery systems?
Large volume parenterals
Syringes
Y-site administration
How does the stability of drug delivery systems depend on environmental conditions?
How does this affect home vs clinical settings?
The stability and expiration dating of a drug depends on temperature which affects storage.
Temperature varies in different environments so proper storage is essential to maintain effectiveness and prevent degradation.
Clinical Setting
Drugs should remain stable at the temperature they will be stored and administered at.
Stability testing ensures the drug remains effective throughout its use in hospitals or clinics.
Home Setting
Medications used at home (e.g., infusions, injections) require a maximum expiration date based on typical home storage conditions.
Sterility Limitations in Drug Handling
Even with the best aseptic (sterile) techniques, contamination can still happen.
How To reduce the risk?
If the drug is not used immediately, it should be stored at ≤40°C to slow microbial growth.
If the drug is intended for prompt use, it can be kept at room temperature, but it should be administered as soon as possible to maintain sterility.
