Stability of pharmaceutical products is important to make those stable, safe and effective for a long time. When it comes to antibiotics, vaccines or other injectables, these must remain chemically and physically stable from the manufacturing stage to administration. Unlike the oral dosage forms, injectables bypass the body’s natural filters; therefore, any degradation product can lead to serious health consequences.
In this article, we will explore why the stability of products is important for injectables, the testing required and the factors affecting the stability of injectable products so that pharmaceutical companies can ensure product safety and compliance.
Injectables must be stable in following five areas.
1. Chemical Stability: There should not be any significant degradation in active pharmaceutical ingredient of the product.
2. Physical Stability: There should not be any physical change in the product like color and appearance any precipitation or separation.
3. Microbiological Stability: Microbial stability means product should remain sterile and free from any contamination throughout its shelf life.
4. Therapeutic Stability: Product should remain stable in its intended therapeutic use and effect.
5. Toxicological Stability: Product should not have any toxic effect due to any degradation product throughout its shelf life.
Injectables are always administered directly into the bloodstream, muscles or tissues that’s why product must be free from impurities and contamination.
1. Safety: Degradation of product can produce toxic byproducts that cause adverse reactions to the patients consuming it.
2. Efficacy: Unstable drugs may lose their potency and therapeutic values which may decrease the efficacy of the product.
3. Regulatory Compliance: Regulatory agencies like the FDA and EMA require stability study data to approve injectable drugs for human use.
4. Supply Chain Integrity: The stable injectable product can be transported safely and stored under a suggested range of atmospheric conditions.
Long-term: 25°C ± 2°C / 60% RH ± 5%
2. Buffer System: The choice of a buffer used to stabilize the pH of the formulation is important. Because a poor choice of buffer can cause salt precipitation and result in an unsterilized injectable product.
3. Excipients: Interaction between excipients and active pharmaceutical ingredients in product plays an important role in product stability. Some excipients may interact negatively with APIs forming degradation products over time.
4. Solvent Type: Solvents like WFI, saline or alcohol-based solvents used to dissolve active materials can cause stability issues in injectable products.
2. Stopper Compatibility: Interaction of the product with the rubber stoppers used in injection vials must be tested and should not have any reaction.
3. Light Sensitivity: Some drug products are light sensitive and can degrade in the presence of light.
2. Humidity: Moisture affects the stability of fridge-dried products.
3. Oxygen Exposure: In the presence of oxygen, drug products may degrade producing impurities.
The stability of injectable drugs is not just a regulatory requirement, it is an important indicator of the safety, quality and efficacy of drug products. Companies must do enough research from choosing the right buffer system to appropriate packaging to make the products reliable for a longer time. Pharmaceutical professionals must always be cautious during the manufacturing of injectables because a minor error can have huge health consequences.
In this article, we will explore why the stability of products is important for injectables, the testing required and the factors affecting the stability of injectable products so that pharmaceutical companies can ensure product safety and compliance.
What Is Drug Stability?
It is a very common question but it is important to describe here because stability of injectable products means a lot. A small quantity of an impurity can have a big impact on the patient's health and safety because injections are directly administered into the patient’s bloodstream. Stability of product refers to the ability of the product to remain stable physically, chemically, microbiologically as well as its therapeutic properties throughout its shelf life. Injectables must be stable in their pH, sterility, appearance and potency.Injectables must be stable in following five areas.
1. Chemical Stability: There should not be any significant degradation in active pharmaceutical ingredient of the product.
2. Physical Stability: There should not be any physical change in the product like color and appearance any precipitation or separation.
3. Microbiological Stability: Microbial stability means product should remain sterile and free from any contamination throughout its shelf life.
4. Therapeutic Stability: Product should remain stable in its intended therapeutic use and effect.
5. Toxicological Stability: Product should not have any toxic effect due to any degradation product throughout its shelf life.
Why Stability Matters in Injectables
Injectables are always administered directly into the bloodstream, muscles or tissues that’s why product must be free from impurities and contamination. 1. Safety: Degradation of product can produce toxic byproducts that cause adverse reactions to the patients consuming it.
2. Efficacy: Unstable drugs may lose their potency and therapeutic values which may decrease the efficacy of the product.
3. Regulatory Compliance: Regulatory agencies like the FDA and EMA require stability study data to approve injectable drugs for human use.
4. Supply Chain Integrity: The stable injectable product can be transported safely and stored under a suggested range of atmospheric conditions.
Stability Testing for Injectable Products
Stability study of pharmaceutical products is carried out during the development of the product and after commercial production. Following are some common tests that are done during stability testing.A. Types of Stability Testing
1. Accelerated Stability Testing
As its name shows, the drug is exposed to high temperature and humidity to predict its shelf life in a shorter period of time. Regulatory agencies recommend doing this type of stability testing.2. Long-Term Stability Testing
This testing is conducted under the recommended storage conditions to assess real-time shelf life of the product.3. Stress Testing
Product is exposed to extreme conditions like heat, light and pH etc. to identify the degradation impurities developed in the product in such conditions.4. Freeze-Thaw Testing
In Freeze-Thaw testing product is checked for its stability by a cooling and heating cycle. This freezing and heating temperature cycle is repeated many times.B. Storage Conditions
Accelerated: 40°C ± 2°C / 75% RH ± 5%Long-term: 25°C ± 2°C / 60% RH ± 5%
Factors Affecting the Stability of Injectable Drugs
The degradation of a drug product is always triggered by any factor. Most of the time, it is an internal factor while sometimes it is done by any external factor.A. Formulation-Related Factors
1. pH: A slight change in pH of the injection formulation can cause hydrolysis of the API in the product.2. Buffer System: The choice of a buffer used to stabilize the pH of the formulation is important. Because a poor choice of buffer can cause salt precipitation and result in an unsterilized injectable product.
3. Excipients: Interaction between excipients and active pharmaceutical ingredients in product plays an important role in product stability. Some excipients may interact negatively with APIs forming degradation products over time.
4. Solvent Type: Solvents like WFI, saline or alcohol-based solvents used to dissolve active materials can cause stability issues in injectable products.
B. Packaging Material
1. Glass vs. Plastic: Glass vials are chemically non-reactive but plastic may leach chemicals. Therefore, packing materials should be selected carefully.2. Stopper Compatibility: Interaction of the product with the rubber stoppers used in injection vials must be tested and should not have any reaction.
3. Light Sensitivity: Some drug products are light sensitive and can degrade in the presence of light.
C. Environmental Conditions:
1. Temperature: Heat always accelerates the degradation of drug products.2. Humidity: Moisture affects the stability of fridge-dried products.
3. Oxygen Exposure: In the presence of oxygen, drug products may degrade producing impurities.
How Manufacturers Ensure Stability of Injectable Products
A. Formulation Development
The right excipients, preservatives, stabilizers and pH are selected through a trial and error approach to create a stable product.B. Lyophilization
Freeze drying method or lyophilization is used to improve the stability of unstable drugs. This method removes water from the product which works as a common degradation catalyst.C. Packaging Optimization
Inert materials like borosilicate glass and gas-filled seals prevent the product from exposure to oxygen and moisture. It helps to minimize the product and degradation.D. Controlled Manufacturing
Implementation of good manufacturing practices in the manufacturing area ensures repeatability and minimizes the risk of contamination.E. Quality Control Testing
Testing product for sterility, particulate matter and potency of every batch helps to ensure the continued stability of the product.Regulatory Guidelines on Injectable Stability
All regulatory agencies require strong stability testing for pharmaceutical products.- US-FDA requires stability data as a part of Investigational New Drug (IND) and New Drug Application (NDA) submissions.
- ICH guidelines have a harmonized approach for stability testing and its documentation.
- WHO guidelines also require stability data for public health and vaccine distribution.
Case Study: Stability Failure in Injectable Drugs
A pharmaceutical giant recalled several batches of injectable antibiotics in 2018, due to presence of visible particulate matter. The root cause was the glass delamination due to the incompatibility between drug product and glass vials.The stability of injectable drugs is not just a regulatory requirement, it is an important indicator of the safety, quality and efficacy of drug products. Companies must do enough research from choosing the right buffer system to appropriate packaging to make the products reliable for a longer time. Pharmaceutical professionals must always be cautious during the manufacturing of injectables because a minor error can have huge health consequences.
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