What determines the shelf life of softgel capsules?
Softgels have unique considerations that affect their stability and their shelf life.
Drawing from our own experience in pharmaceutical research and development, this article addresses one of the most frequently asked questions about softgel formulations: How long is typically the shelf life of softgel capsules and what are the limiting aspects to it?
The Science Behind Expiration Dates
Let’s start with what expiration dates are and why they exist. Established in 1979, the FDA's requirement for drug manufacturers to include expiration dates for all pharmaceutical products. These dates were introduced to protect patient safety and provide clear guidance about medication quality over time.
These dates aren't arbitrary. Rather, they're established through strict regulatory guidelines that track critical quality parameters. Indeed, manufacturers conduct extensive stability testing to guarantee both safety and efficacy throughout a product's shelf life.
For new products, the requirements for stability testing are described in ICH guideline Q1A. In order to determine their shelf life, drug products have to be stored at defined conditions depending on the prevailing conditions in the climatic zone of the target territories and tested at defined intervals during this period. For example, most European countries are in climatic zone I or II, therefore the product has to remain stable over the entire shelf life while stored at 25°C/60% r.h. (for climatic zone II). In addition, storage at so-called intermediate (30°C/65%r.h.) and accelerated conditions (40°C/75%r.h.) for shorter periods provide additional data -and faster. These data are in some cases are representative for the behavior at long-term conditions. However, for softgels especially results from accelerated testing may be overdiscriminating and not always representative for what happens during ambient storage.
When it comes to softgel capsules, expiration dates aren't simply about the active ingredients inside. What’s more, the capsule shell itself plays a crucial role in the product's stability and shelf life. Understanding how capsules age requires considering both the shell and its contents.
Moreover, beyond basic parameters like assay and appearance, critical factors such as dissolution performance and shell integrity must meet strict specifications throughout the product's lifetime. Contrary to some misconceptions, pharmaceutical companies actively strive to achieve the longest possible shelf life. There's no benefit in artificially short shelf lives.
How Softgel Age
Understanding softgel stability requires examining the interaction between shell and fill. Unlike tablets, softgels represent a complex delivery system where the shell serves not just as a container, but as an integral part of the drug delivery mechanism. These critical factors determine their stability:
Shell composition: the rupture and dissolution of the capsule shell is the first limiting aspect to the delivery of the active ingredient. The shell therefore plays a significant role in the definition of the shelf life of a softgel, and changes in the solubility of the capsule shell often impact the shelf life of the capsules.
Fill mass and drug substance stability: the capsule fill contains the active ingredient. Its stability and interaction with the shell are therefore crucial to the product's stability. Factors like the solubility of the drug in the matrix, compatibility with the excipients, and tendency to degradation due to oxidation, hydrolysis, or light for example play a role in the stability of the drug product.
Environmental conditions: the temperature and humidity of storage are critical for all dosage forms, but softgels are especially vulnerable under temperature and humidity stress. Standard gelatin-based capsules can´t be expected to be stable at temperatures above 40 degrees alone due to the properties of gelatin- they would become very soft and physically unstable. They are especially sensitive to increased humidity - the capsule shell acts like a sponge and may take up water until equilibrium with the environment is reached. Such an increase in shell water content typically leads to physical instabilities, e.g. softening and sticking, but can also accelerate the degradation of the drug substance.
The Most Common Instabilities in Softgels that Limit Shelf Life
Instabilities in softgels are often connected to changes in physical properties, e.g. increase or decrease of hardness, delay in dissolution/disintegration time, or are inherent to the properties of the drug substance.
However, other instabilities that are often problematic in tablets, such as oxidative degradation of the drug substance, can be handled well in softgels. Oxidative degradation can be limited to a large extent by the use of appropriate shell formulations and processing aids, e.g. inert gases. This is especially helpful because the capsule fill in softgels is liquid, and thus easier to handle under a protective atmosphere—which is not as easy a process compared to powders.
Understanding Critical Quality Attributes for Softgel Capsules
Determining softgel expiration dates involves more than just measuring the assay of the active ingredient. Critical quality attributes for softgels also include dissolution and disintegration, which ensure the product releases its contents properly, and shell integrity evaluation, which confirms the capsule maintains its protective function. Other factors affect physical stability, e.g. hardness and appearance.
As for all oral dosage forms, strict guidelines are applied concerning related substances and contaminants, and microbiological quality. Contrary to the common belief that the main determining factor for the expiry date is the assay of the drug substance or even the formation of (potentially toxic) degradation products, in fact any of these factors can be limiting for the shelf life of the product. Often in softgels, while the assay and degradation substances remain within the strict specification limits, the dissolution may be delayed significantly during storage and be in fact the limiting factor for the shelf life.
Interested in learning more about quality control tests for softgel capsules? Don’t forget to read our e-book!
The Critical Role of Storage Conditions for Softgel Capsules
The shelf life of softgel capsules depends heavily on storage conditions, with environmental factors playing a crucial role in maintaining product stability. Two key aspects determine how storage affects softgel integrity:
1.Storage environment: The location where softgels are kept significantly impacts their stability. Bathroom medicine cabinets and kitchen storage areas pose particular risks due to:
Frequently increased storage temperatures may accelerate the degradation of the drug substance and lead to physical instabilities
High humidity levels that can alter moisture content and also lead to physical and chemical instabilities
For some products, exposure to light may be an issue. They are typically labeled accordingly
For optimal stability, softgels should be stored in temperature-controlled environments at conditions indicated on the package
2. Packaging materials: The original packaging is critical in protecting softgels from environmental stressors. These containers are specifically designed with materials selected for optimal moisture barriers. As opposed to tablets, packaging materials which limit the permeation of oxygen are typically not required for softgels. The expiry dates given on the package only apply if the product is stored in the original container.
Making Informed Decisions About Expired Softgel Capsules
For prescription medications and essential therapeutic products, adherence to expiration dating is crucial. While patients often fear that expired products may be toxic, this is rarely the case. The main risk is reduced efficacy which could have serious health implications, making it imperative to maintain current stock and replace products before expiration. The potential consequences of reduced therapeutic effect outweigh any economic benefits of extending use beyond the labeled date.
How we can support your soft capsule development project
Our team offers the following:
+ Risk-based formulation development concepts in consideration of the entire soft capsule
+ Defining appropriate control strategies for softgel capsules
+ Preparation of state-of-the-art CMC and development documentation for softgel capsules
