The Science of Drug Stability

How to ensure long-lasting efficacy

Did you know that even the most effective drug can fail if it's not stored properly? Stability is a critical aspect of any pharmaceutical product. It ensures that a drug remains effective, safe, and reliable throughout its shelf life. For pharma business owners, understanding drug stability isn't just a regulatory necessity—businesses must maintain their market reputation and avoid costly recalls.  

In this blog, we’ll explore the science of drug stability, share key factors affecting it, and share actionable storage tips to maximize shelf life. 

What is Drug Stability?

Drug stability refers to a product’s ability to maintain its physical, chemical, therapeutic, and microbiological properties throughout its shelf life. A stable drug ensures: 

• Efficacy: The active ingredient remains effective. 

• Safety: No harmful by-products form over time. 

• Compliance: Regulatory requirements are met.

Example: A vitamin C tablet exposed to moisture may degrade, reducing its potency and therapeutic value.  

Key factors affecting Drug Stability:

Temperature 

• High temperatures can cause APIs to degrade.

• Some drugs require refrigeration, while others are sensitive to freezing. 

Humidity 

• Excess moisture can lead to hydrolysis or microbial growth. 

• Proper packaging, like desiccants or moisture-proof seals, is essential. 

Light 

• UV and visible light can cause photodegradation of APIs and excipients.

• Amber or opaque containers help protect light-sensitive drugs. 

Oxygen 

• Oxidation reactions can render drugs ineffective. 

• Packaging in nitrogen-filled or airtight containers minimizes exposure. 

Packaging Materials 

• The choice of material (glass, plastic, foil) impacts stability.

• Leaching from poor-quality packaging can compromise drug safety.  

  

  Type of Stability Testing

  Stability testing ensures that drugs maintain their quality and effectiveness throughout their shelf life. In the early stages, accelerated testing under high temperatures and humidity helps identify potential degradation. Later, testing under near-normal storage conditions determines the product's shelf life and expiration date. The goal is to ensure the drug remains safe and effective until fully consumed. Stability testing is categorized into four main types based on purpose and methods:

  Accelerated Stability Testing: Accelerated stability testing is a way to predict how long a product (like a medicine) will remain effective by exposing it to tough conditions, such as high temperatures. This process speeds up the natural breakdown of the product so scientists don’t have to wait years to see how it changes over time.

  Purpose: To estimate the product's shelf life and compare different formulations quickly during development.

  Conditions: High stress like heat, moisture, light, shaking, or different pH levels is used to simulate what might happen over time.

  Testing Process: In this method, Samples are stressed (e.g., heated) and then, they are stored in a fridge to "pause" further changes. Finally, all the samples are analyzed together to ensure consistency.

  Result: The product's stability is checked by comparing how much of the active ingredient remains compared to an unstressed (normal) sample.

  Example:

  Imagine a liquid vitamin supplement. Normally, it might take two years to see if the vitamin loses its potency. Instead, scientists heat the sample to 40°C (much hotter than room temperature) for a few weeks. This speeds up the breakdown process. By measuring how much vitamin is left, they can predict how long the product will last under normal conditions.

  If the product contains delicate components like proteins, they use less intense heat because too much heat can destroy the proteins instead of just simulating aging.

  Testing at multiple temperatures (e.g., 25°C, 30°C, 40°C, and 50°C) gives more reliable results for shelf-life predictions.

  Real-Time Stability Testing: Real-time stability testing checks how a product degrades over time under normal storage conditions, like room temperature or refrigeration. It helps determine how long the product stays effective and safe to use.

  Purpose: To monitor the product's actual behavior over its shelf life under recommended storage conditions.

  Duration: Testing lasts for a long period (months or years) to ensure real degradation can be seen, not just normal variations.

  Process: The Data is collected at regular intervals to spot patterns and a reference batch with known stability is tested to compare results and ensure accuracy.

  Reliability Factors: The stability of the testing reagents is checked to avoid false results. Equipment is monitored for consistent performance to prevent errors from machine drift or reagent changes.

  Example:

  Imagine testing a cream that needs to be stored at 25°C. Samples are stored under these conditions and tested every 3 months. If the cream starts separating or losing effectiveness after 18 months, this shows its shelf life is 18 months. Including a reference cream that is already known to be stable helps confirm the results are accurate and not due to testing errors.

  Retained Sample Stability Testing: Retained sample stability testing ensures that a product stays stable and effective throughout its shelf life by testing samples stored under controlled conditions.

  Purpose: To continuously confirm the product's stability after it's launched in the market.

  Sample Selection: At least one batch is tested yearly and for companies selling over 50 batches annually, two batches are tested. When a product is new, every batch may be tested at first, but this is later reduced to a small percentage (2–5%).

  Testing Schedule: Samples are tested at regular intervals (e.g., 3, 6, 12, 24, and 60 months for a product with a 5-year shelf life).

  Methods:

  • Controlled Testing: Uses storage conditions like room temperature or refrigeration to get consistent results (constant interval method).

  • Real-World Testing: Tests products taken from the market to see how they perform under actual conditions, like transportation and varying temperatures.

  Example:

  For a cough syrup with a shelf life of 3 years, samples from the factory are tested every 6 months for signs of changes in color, taste, or potency. If the syrup is sold widely, some samples might be taken from store shelves to see how well it holds up in real-world conditions like heat or shaking during shipping. This ensures the product stays effective for the customer.

  Cyclic Temperature Stress Testing: Cyclic temperature stress testing checks how a product handles temperature changes, similar to what it might experience during real-world storage. This method isn’t commonly used for products already on the market.

  Purpose: To see if temperature fluctuations affect the product's quality or stability.

  What It Mimics: Simulates daily temperature changes (e.g., hotter during the day, cooler at night).

  How It Works:

  • The temperature range is based on the product’s storage requirements and how stable it is.

  • Testing usually involves 20 cycles of temperature changes to see if the product can handle repeated variations.

  Example:

  Imagine a bottle of eye drops meant to be stored at 25°C. During testing, the temperature is cycled between 15°C at night and 35°C during the day, repeating this 20 times. This helps determine if the eye drops stay effective even when exposed to temperature changes, such as when stored in a car or an air-conditioned room alternately. 

  Potential adverse effects of instability in pharmaceutical products

  

  
  

  Practical Storage Tips

  • Always adhere to storage instructions provided on the label (e.g., "Store below 25°C").

  • Use refrigerators or cold storage for temperature-sensitive drugs like biologics.

  • Install humidity monitors in storage areas.

  • Opt for blister packs, foil pouches, or glass containers for maximum protection.

  • Use vacuum-sealed packaging for moisture-sensitive products.

  • Regularly audit inventory and rotate stock using FIFO (First-In, First-Out).

  • Train Your Team, ensure that employees handling drugs understand proper storage protocols, and conduct periodic training on stability guidelines. 

  Emerging Trends in Drug Stability 

  Smart Packaging Solutions: Innovations like temperature indicators and time-temperature integrators help monitor stability in real time. 

  Stabilization Technologies: Techniques like freeze-drying (lyophilization) are used to improve the stability of injectable drugs. 

  Sustainable Packaging: Pharma companies are exploring eco-friendly yet effective packaging materials to reduce environmental impact. 

  How Walter supports Stability Management Drug stability is the cornerstone of product quality and customer trust. By understanding the factors that impact stability and implementing proper storage practices, MSME pharma businesses can ensure their products remain effective and compliant throughout their shelf life.  As a third-party manufacturing partner, we understand the importance of drug stability. Here’s how we help our clients: 

  Comprehensive Stability Testing: We ensure your products comply with regulatory requirements. Advanced Packaging Solutions: We provide custom packaging to protect your products from environmental factors. Tailored Storage Guidelines: We guide MSMEs on optimal storage practices to maintain product efficacy.

  Looking to optimize drug stability for your products? Contact Walter® today for expert guidance and world-class manufacturing solutions. Let’s build a stable future for your business!