All of us have experienced this at least once in our lives where our elders, parents and even friends ask us to check the expiration date before buying the medicine. Ever wondered why there is an expiration date on your medicine packets and what do they mean?
In simple words, it means the medicine is fit for use till that date. It is stable and its quality is maintained.
How is the stability maintained and what is the relation between quality and shelf life?
In this blog we will discuss drug stability factors in detail.
Let us understand the science behind
What Is Drug Stability?
Drug stability refers to how well a pharmaceutical product maintains its
- Chemical identity
- Potency
- Physical appearance, and
- Microbial quality
Throughout its shelf-life.
In simple terms, a stable drug stays safe, effective, and usable for the entire duration written on its label.
When a drug becomes unstable, it may:
- Lose potency
- Change color or texture
- Form toxic degradation products, or
- Fail to deliver the expected therapeutic effect
Why Is Drug Stability Important?
Drug stability is an important quality parameter of any drug product. It directly affects:
Safety
- Unstable drugs may form harmful degradation products.
- E.g.: Tetracycline can form nephrotoxic compounds.
Efficacy
- Reduced strength means the patient receives a lower dose than intended.
Shelf-life
- This determines how long the product can be stored.
Packaging and storage
- The stability of a drug product helps decide if a drug needs
- Refrigeration
- Amber vials
- Desiccants
- Or any other form of special storage.
Regulatory approval
- Stability studies are essential for drug licensing worldwide.
Types of Instability in Pharmaceuticals
| Type of Instability | Description | Examples |
| Chemical | Changes in molecular structure due to reactions | Hydrolysis of aspirin Oxidation of vitamin C |
| Physical | Changes in physical form | Tablet disintegration Cream phase separation |
| Microbiological | Growth of bacteria, fungi, or spores | Contaminated syrups or eye drops |
| Therapeutic | Change in drug effect | Reduced potency from degradation |
| Toxicological | Formation of harmful products | Degraded tetracycline |
These categories help us to understand and predict what may go wrong during storage.
Key Factors Affecting Drug Stability
Below are the major environmental and formulation-related factors that influence how long a drug remains stable.
1. Temperature
Temperature is one of the most critical factors. High temperatures accelerate chemical reactions such as:
- Hydrolysis
- Oxidation
- Dehydration
- Racemization
General rule:
For every 10°C rise in temperature, many degradation reactions double in rate.
Examples:
- Vitamin C oxidizes faster at room temperature than in a refrigerator.
- Probiotics and insulin lose stability quickly if stored above recommended temperatures.
2. Humidity (Moisture)
Moisture affects drug stability especially in hygroscopic and hydrolysis-sensitive drugs.
Effects of humidity include:
- Tablet swelling or disintegration
- Activation of hydrolytic reactions
- Aggregation or clumping of powders
Examples:
Aspirin tablets degrade faster in humid conditions due to hydrolysis into acetic acid and salicylic acid.
3. Light (Photodegradation)
Certain drugs react with UV or visible light. This causes discoloration or loss of potency.
Common light-sensitive drugs:
- Nitroglycerin
- Nifedipine
- Riboflavin
- Chlorpromazine
Solution:
Amber or opaque bottles to block light exposure.
4. Oxygen (Oxidation)
Exposure to oxygen can degrade drugs via:
- Autoxidation
- Free radical formation
- Peroxide formation
Examples:
- Oils and fats become rancid.
- Vitamin A, E, and C oxidize easily.
- Adrenaline darkens upon oxidation.
Prevention:
- Use antioxidants such as BHT or sodium metabisulfite
- Replace air with nitrogen in vials which is known as nitrogen flushing
5. pH of the Formulation
The pH environment influences the rate of
- Hydrolysis
- Oxidation, and
- Ionization
Many drugs have optimal stability only within a narrow pH range.
Example:
Penicillin is most stable around pH 6.0 but degrades rapidly at extreme pH values.
6. Excipients
Additives can affect stability positively or negatively.
- Some excipients cause incompatibility.
- Others enhance stability.
Example:
- Binders
- Solvents
- Preservatives
- Surfactants
- Chelating agents
7. Container and Packaging Material
Packaging protects the product from environmental stress.
Examples:
| Packaging Material | Protection Offered |
| Amber glass | Blocks UV light |
| Blister packs | Protect from moisture |
| Aluminum tubes | Protect light-sensitive creams |
| Desiccant bottles | Absorb moisture |
8. Manufacturing Process
Factors such as
- Drying temperature
- Mixing time
- Sterilization
- Compression force
can impact stability.
For example:
- Over-lubrication during tablet compression may reduce hardness.
- Excess heat during drying can degrade thermolabile drugs.
How Is Shelf-Life Determined?
Pharmaceutical companies conduct stability studies under controlled conditions:
1. Real-Time Stability Testing
- Stored at recommended conditions
- E.g., 25°C, 60% RH
- Monitored for months to years
2. Accelerated Stability Testing
- Higher temperature and humidity
- E.g., 40°C, 75% RH
- Used to predict long-term stability faster
Regulatory guidelines follow ICH standards.
Signs a Drug May Be Unstable
- Change in colour, odour, or taste
- Cloudiness in solutions
- Separation of layers in creams or suspensions
- Crumbling or swelling of tablets
- Gas formation in liquids
- Appearance of precipitates
Patients should always check labels and expiry dates before use.
Tips for Proper Storage
- Keep medicines in cool, dry places unless stated otherwise.
- Avoid bathroom storage. High humidity causes degradation.
- Always close container lids tightly.
- Keep refrigerated medications between 2-8°C.
- Store light-sensitive drugs in amber coloured packaging.
- Don’t freeze medicines unless instructed.
- Always check expiry dates and discard when expired.
Learn And Level Up
The understanding of drug safety is not just important from an industry point of view. It is an important aspect that every pharmacist should be aware of. The knowledge of drug storage and stability is a common question asked in many licensing exams like OPRA. It is an integral part of any working pharmacy and if you’re preparing to become a pharmacist in a country like Australia, you should be well-versed in it.
