Softgel Capsules Explained: The Ultimate FAQ Guide (Part II)
Building on our series, this second part of our softgel capsule FAQ delves into the more technical and scientific aspects of this dosage form. Indeed, while Part I addressed common consumer questions, this section explores the intricate details that pharmaceutical professionals and researchers need to understand for the effective development and production of softgel capsules.
This article addresses some of the most frequently asked questions about softgel capsules from a scientific and industry perspective, providing insights into their manufacturing process, technical properties, and market dynamics. We hope this resource will enhance your understanding of softgel capsules, whether you're a pharmaceutical professional, a researcher, or involved in the production and development of drug products.
1. What is the pH value of softgel capsules?
The pH value measures the hydrogen ion concentration in an aqueous solution. In softgel capsules, the pH value depends on the water-soluble or miscible components, including the drug substance. For capsules containing a 100% lipid fill, the pH value primarily depends on the capsule shell, which is largely determined by the gelatin. Gelatin type A typically has a pH value of 7-9, while type B ranges from 4.7-5.5.
Extreme pH values should be avoided in the shell as they can lead to hydrolyzation of the gelatin protein chains and loss of gel strength. While pH is not usually a critical issue, it should be carefully considered when the active pharmaceutical ingredient (API) has specific pH requirements to avoid degradation.
In general, the pH value of softgel capsules is not fixed, but rather a result of the interaction between the shell and fill components.
2. How do you prevent softgel capsules from leaking?
Leakage in softgel capsules is a common concern that occurs when the capsule shell's integrity is compromised. While damage can theoretically happen anywhere on the capsule, leaks typically occur at the weakest point: the capsule seam.
To avert leakage, it's vital to identify and address the root causes. Here are two of the most common issues and their solutions:
Oversized particles in the fill: Large particles can get trapped in the seam during encapsulation, creating channels for the fill to leak. The solution is straightforward: reduce the particle size in the fill material.
Unsuitable processing parameters: These can lead to thin, weak seams. Adjusting the process parameters can help, but this approach has its limits. Some fill materials are known to interfere with proper seam formation. In these cases, selecting the right shell formulation becomes key.
Preventing leakage is a complex challenge that requires attention throughout the formulation and manufacturing process. It starts with carefully formulating the shell and fill materials, ensuring they're compatible and stable. By addressing these factors, manufacturers can significantly reduce the risk of leakage and produce high-quality softgel capsules.
Interested in knowing more about shell development? Read our e-book about that topic:
3. Do you need to reject the entire batch if one capsule is leaking?
The properties of the fill mass in some products may lead to leakers despite all precautions and optimizations. In such cases, manufacturers typically employ additional rigorous visual control of the entire batch to sort out leaking capsules.
While it is classified as a critical defect, it does not mean that leakers should lead to the destruction of the entire batch.
If any capsules are leaking or contaminated, they should be removed; if leaking occurs in a primary bulk packaging container, for example, in Al bags, based on their SOP, the CMO may decide to either discard the affected bags or to resort to them.
4. What is the role of CDMOs (Contract Development and Manufacturing Organizations) in softgel capsule production and why are they important?
CDMO stands for Contract Development and Manufacturing Organization. In the pharmaceutical industry, a CDMO is a company that provides drug development and manufacturing services on a contract basis. For softgel capsules, a CDMO might offer services such as:
Formulation development
Scale-up and manufacturing
Analytical testing and quality control
Regulatory support
Packaging and distribution
Working with a CDMO can provide pharmaceutical companies with specialized expertise and manufacturing capabilities for softgel production. Notably, a substantial portion of the softgel market and associated know-how is concentrated in the hands of CDMOs. This concentration means that while pharmaceutical companies can access advanced capabilities through partnerships, they may also lean heavily on CDMOs for softgel projects. It’s a dynamic that creates both opportunities and challenges, as companies counterbalance the benefits of CDMO expertise with the need to maintain their core competencies in drug delivery technologies.
Interested in knowing more about CDMOs? Read our article about choosing the right CDMO partnership
5. Who are the major softgel capsule manufacturers?
Several companies specialize in softgel capsule manufacturing, including:
Various smaller companies specialize in different types of manufacturing, and it may be worth evaluating them for specific requirements.
6. How big is the softgel market?
These players are part of a greater softgel capsule ecosystem which is expected to keep growing. Indeed, the global softgel capsules market is currently valued at around USD 4.88 billion, and industry analysts project a growth of 9.2% for the foreseeable future—a robust expansion in this sector.
Several factors have driven this growth, including increasing consumer preference for easy-to-swallow dosage forms, the rising popularity of nutraceuticals and dietary supplements, and advancements in softgel technology that allow for a broader range of applications. Additionally, the growing pharmaceutical industry in emerging markets and the increasing adoption of softgels for over-the-counter medications contribute to this positive market outlook.
7. What is the cost of manufacturing a softgel capsule?
The cost of manufacturing softgel capsules can vary significantly depending on several key factors. The scale of production plays a crucial role, as larger batches often benefit from economies of scale. The complexity of the formulation is another important consideration, with more intricate or specialized formulations typically incurring higher costs.
Raw material costs can fluctuate based on market conditions and the required ingredients. Regulatory requirements also impact the general cost, as compliance with different standards may necessitate additional testing or documentation.
Typically, all things being equal, manufacturing costs for softgels can be up to 1.5 times higher than comparable tablets in bulk production. However, this cost difference often narrows at the consumer level. For example, the price difference between Nurofen tablets and Nurofen softgels is less pronounced for the end consumer.
It's important to note that pharmaceutical pricing is heavily regulated by local authorities, leading to significant variations in patient/consumer prices from country to country. For instance, Voltaren Dolo tablets might cost €7.25 for 20 tablets, while the softgel version could be priced at €8.60 for 20 capsules in the same market.
Given these variables, it's challenging to provide a one-size-fits-all cost estimate. For accurate pricing, it's recommended that you consult directly with manufacturers or Contract Development and Manufacturing Organizations (CDMOs), as costs are often project-specific and tailored to individual requirements. Additionally, when considering the overall cost-benefit analysis, factors such as bioavailability, patient preference, and market positioning should be considered alongside pure manufacturing costs.
Tumble drying of softgel capsules
8. What drying process is better: tumble drying or tray drying?
During the drying process, the excess water in the capsule shell must be removed to achieve the physical stability of the capsules. During drying, it is reduced from approximately 35-40% at the time of encapsulation to 6-12% at the end of the drying. In all cases, the initial drying stage takes place in tumblers to avoid deformation of the wet capsules.
The main process variables during drying are the humidity and temperature of the ambient air and the air volume. While humidity and temperature can be maintained at similar levels during both tumble and tray drying, the airflow may be different; however, in most cases, there is not a significant difference between the two types of used equipment.
However, tray drying may be advantageous in some cases, such as when inspection for leakers is required or when long processes are involved.
9. How long does the drying process take?
The drying duration is strongly dependent on the product characteristics and can be anywhere between 20 hours and several days, up to a week.
10. What materials are used in softgels?
Softgel capsules primarily consist of the following:
Gelatin: Derived from animal collagen, typically from bovine or porcine sources. It forms the elastic shell of the capsule and is responsible for its unique properties. Gelatin is chosen for its ability to form a stable, dissolvable film.
Water: Used in processing and remains a key component in the final product. It helps form the gelatin film and contributes to the capsule's flexibility.
Plasticizers: These include materials such as glycerin or sorbitol, which improve the flexibility and durability of the capsule shell. They prevent the capsule from becoming brittle and help maintain its integrity during storage.
Optional additives: These may include colorants for product identification, preservatives to extend shelf life, or opacifiers to protect light-sensitive contents. Flavorings might also be added to mask unpleasant tastes.
The fill material can vary widely depending on the specific drug or supplement but often includes oils, suspensions, or solubilized active ingredients.
Interested in knowing more about shell development? Read our e-book about that topic here:
11. Is it easier to swallow softgels or tablets?
Softgel capsules are generally considered easier to swallow than tablets. This is due to their smooth, elastic outer shell, which allows them to slide down the throat more easily. The gelatin shell also becomes slippery when wet, further facilitating swallowing, and the smooth, oval shape of softgel capsules facilitates easier swallowing compared to tablets or hard capsules, which can improve patient compliance. However, it’s worth noting that individual experiences may vary, and some patients may find tablets or other dosage forms preferable.
Interested in knowing more about the difference between softgel capsules and tablets? Read our article about the differences
Want more advice about which delivery form is right for you?
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