Drug stability refers to a drug’s ability to maintain the same properties and characteristics it had at the time of manufacture over its storage period. This includes maintaining its chemical, physical, microbiological, therapeutic, and toxicological integrity.

Instability can show up in several ways, such as:

• Microbial contamination of liquid suspensions
• Discoloration of tablets
• Degradation during storage that reduces drug efficacy

Stability testing is a regulatory requirement for all drugs.

Physical stability of drugs

A drug’s physical state affects important performance factors such as solubility, absorption, and potency. Many physical changes can be prevented by storing drugs in well-closed containers and protecting them from direct light.

A few examples of loss of physical stability include the following:

• Drugs present in the amorphous state may easily degrade and crystallize during storage, affecting solubility and toxicity. For example, amorphous nifedipine crystallizes under high humidity.
• In a saturated solution, a temperature change may cause the solute to precipitate.
• Loss of volatile substances used in certain drug forms like elixirs, spirits, and drugs containing aromatic water, e.g., nitroglycerine.
• Water loss may increase the concentration of the active drug and lead to the degradation of water-containing drug forms like ointments, pastes, and creams.
• Suppositories made from hydrophilic substances like glycerine, poly-ethylene glycol, etc., may absorb atmospheric water and lose their original physical form.
• Color changes in a drug can occur due to exposure to light or pH changes.

Chemical stability of drugs

Chemical stability describes how well a drug resists chemical reactions that can reduce potency or produce harmful (toxic) breakdown products. Common reactions that affect drugs include oxidation, hydrolysis, dehydration, chelation, polymerization, and isomerization.

Here are a few common examples:

• Epinephrine oxidizes to a red-colored product, which makes it ineffective.
• Drugs such as aspirin, penicillins, and cephalosporins can undergo hydrolysis when pH changes.
• Many drugs are most stable near neutral pH.
• Exposure to light and high temperatures can accelerate oxidation.

Microbiological stability of drugs

Microbiological stability refers to a product’s ability to resist microbial contamination during manufacturing, storage, and use.

Contamination is more likely when:

• The drug contains water (which supports microbial growth)
• Natural polymers used in manufacturing carry microbial contaminants

Contamination may originate from raw materials, manufacturing instruments, storage containers, or personnel. Common contaminants include molds, micrococci, Pseudomonas, and E. coli.

Drug stability and Insulin

Insulin is a commonly used drug available in injectable forms. Storage conditions strongly affect insulin potency.

Key storage points include:

• Store insulin in a refrigerator at approximately 36°F to 46°F.
• If unopened and stored under refrigeration, insulin maintains potency until the expiration date on the package.
• Insulin in manufacturer-supplied vials or cartridges (opened or unopened) may be left unrefrigerated at 59°F to 86°F for up to 28 days and still work.
• If an insulin product has been altered (for example, diluted or removed from the manufacturer’s original vial), it should be discarded within two weeks.
• Frozen insulin should not be used.
• Insulin should never be exposed to direct sunlight.
• At pH values below five and above eight, insulin degrades relatively fast.

Drug stability and oral suspensions

Oral suspensions have high moisture content. This increases the risk of:

• Microbial contamination
• Drug degradation
• Loss of moisture (which can concentrate the drug and increase the dose per volume)

Most suspensions are stable for fourteen days after reconstitution when refrigerated between 36°F and 46°F.

Name of oral suspension	Expiration date after reconstitution
Amoxicillin and Clavulanate Potassium for oral suspension, Augmentin	Suspension must be refrigerated. Discard after 10 days.
Amoxil, amoxicillin oral suspension	Store at room temperature or in the refrigerator. Discard after 14 days.
Cefdinir oral suspension, Omnicef	Store at room temperature. Discard after 10 days.
Cephalexin oral suspension, Keflex	Refrigerate after reconstitution. Discard after 14 days
Azithromycin, Zithromax oral suspension	Store constituted suspension between 5-30 degree Celsius and discard when full dosing is completed, maximum up to 10 days
Zmax (azithromycin extended release) oral suspension	Store constituted suspension at preferably 25 degree Celsius and discard after 12 hours. Do not refrigerate or freeze.
Cleocin Pediatric for oral suspension, Clindamycin	Store at room temperature and discard two weeks after reconstitution. Do not refrigerate the reconstituted solution.

Vaccine stability

Proper vaccine storage is essential to maintain vaccine efficacy. A cold chain is a temperature-controlled supply chain that includes all vaccine-related equipment and procedures.

The cold chain:

• Begins with the cold storage unit at the manufacturing plant
• Continues through transport and delivery
• Includes correct storage at the provider facility
• Ends when the vaccine is administered to the patient

Overexposure to heat, cold, or light can decrease vaccine efficacy. Storage temperature depends on the vaccine type, so manufacturer recommendations must be followed.

General storage principles include:

• Vaccines licensed for refrigerator storage should be stored at 2°C-8°C (36°F-46°F).
• Certain lyophilized (freeze-dried) vaccines, such as varicella (chicken pox), are stored frozen.
• Vials and manufacturer-filled syringes should always be stored in their original packaging.
• Vaccines and diluents with the earliest expiration dates should be kept in front of those with later expiration dates.

Beyond use date or BUD for vaccines

BUD is the final date or time beyond which an “altered” vaccine can be used. The BUD is different from the expiry date of the vaccine.

A vaccine may be considered “altered” when:

• It is moved between storage conditions (for example, from a deep freezer to a refrigerator, or from either of these to room temperature)
• It is mixed with a diluent
• A vial is punctured

Administering a vaccine after the BUD is a vaccine administration error and may decrease the vaccine’s efficacy.

COVID vaccine storage requirements

Name of vaccine	Storage requirements
Pfizer-BioNTech COVID-19 vaccine for ages 6 months to 4 years	Store vaccine between -90 and -60 degrees Celsius (-130 and -76 degrees F).
BUD - Store unpunctured vials between 2-8 degrees Celsius (36-46 degrees F) for up to 10 weeks, or between 8-25 degrees Celsius (46-77 degrees F) for up to 12 hours.
Discard punctured vials after 12 hours.
Pfizer-BioNTech COVID-19 vaccine for ages 5 to 11 years	Store vaccine between -90 and -60 degrees Celsius (-130 and -76 degrees F).
BUD - Store unpunctured vials between 2-8 degrees Celsius (36-46 degrees F) for up to 10 weeks, or between 8-25 degrees Celsius (46-77 degrees F) for up to 12 hours.
Discard punctured vials after 12 hours.
Comirnaty vaccine for ages 12 years and above	Store vaccine between 2-8 degrees Celsius (36-46 degrees F).
Do not freeze.
BUD - May be stored between 8-25 degrees Celsius (46-77 degrees F) for up to 12 hours.
Once activated, use within 4 hours.
Novavax COVID-19 vaccine	Store vaccine between 2-8 degrees Celsius (36-46 degrees F).
Do not freeze
Moderna COVID-19 vaccine for ages 6 months to 11 years	Store vaccine between -50 and -15 degrees Celsius (-58 and 5 degrees F).
BUD - Store between 2-8 degrees Celsius (36-46 degrees F) for up to 60 days, or between 8-25 degrees Celsius (46-77 degrees F) for up to 12 hours.
Spikevax COVID-19 vaccine for ages 12 years and above	Store vaccine between -50 and -15 degrees Celsius (-58 and 5 degrees F).
BUD - Store between 2-8 degrees Celsius (36-46 degrees F) for up to 60 days, or between 8-25 degrees Celsius (46-77 degrees F) for up to 12 hours.

Always refer to the latest manufacturer product information for best use practices. Recommendations for storage and use may change as new batches are released. Once thawed, vaccines should not be refrozen.

Comparing expiration date with shelf life of a drug

• Expiration date: The date by which the manufacturer guarantees the drug’s potency and safety. Ideally, drugs should not be used after the expiration date. Some drugs may still maintain potency for a while after the expiration date, and some degrade to toxic products after the expiration date. The expiration date may contain letters or numbers. The FDA recommends including a year, month, and date in a YYYY-MM-DD format (e.g., 2027-02-01) or a YYYY-MMM-DD format (e.g., 2027-FEB-01). If space is limited on the package, a YYYY-MM (2021-01) or YYYY-MMM (2021-JAN) format can be used. The parts should be separated by a hyphen or by a forward slash.

• Shelf life: This refers to the quality of a drug. Although drugs past their shelf life are not necessarily toxic, they may not be effective. Shelf life is affected by storage conditions such as heat, light, and moisture.