Soft capsules, also known as softgels, are mainly used as a vessel for oil-based liquids or paste- like fills and have grown in popularity with time because of ease of absorption. The market for softgels is expected to grow 9% compounded annually during the next 6 years and, by 2028, is estimated to be worth $9.1 billion.
Owing to its natural properties, functional benefits and suitability for immediate release dosing, gelatin is by far the main gel-forming agent used in softgel production.
Launched in 2018, StabiCaps features tailored gelatins that offer superior shell stability and active pharmaceutical ingredient (API) release levels when compared with standard gelatins. With strong shell stability and the capacity to dissolve effectively with time, StabiCaps minimises the risk of crosslinking reactions in softgel production, a common challenge faced by nutraceutical and pharmaceutical manufacturers when using reactive fills.
AKA: Can you provide a brief overview of cross linking and the problems it causes?
PAT: Crosslinking impacts the stability of various dosage forms. For Rousselot, this is particularly relevant to softgel applications. We’ve done extensive research to fully understand how and why crosslinking occurs. This has helped us identify the different parameters that impact the tendency of gelatin to crosslink. These parameters are linked to storage conditions, the presence of
aldehydes or antioxidants (polyphenols) in APIs or nutraceutical fillings, as well as the use of complex fillings with multivitamins, multi-minerals, metallic ions or combinations of these.
Gelatin is a protein polymer and, in certain conditions with specific chemical entities, it can become crosslinked because of chemical reactions that impact its ability to dissolve. A softgel is basically a gelatin shell that’s plasticised. Inside, there is a fill that contains the API. Fills are quite complex because they incorporate different ingredient types together, with some of these exhibiting a crosslinking effect on the gelatin shell.
Crosslinking isn’t a highly frequent event; but, when it happens, it’s a significant issue. If you are a formulator working with softgels and you are looking to formulate a fill, you need to optimise each step of the formulation process as well as ensure the long-term stability of your product. This procedure takes time.
After formulation, the softgel prototype will go into storage for a few months; this step allows to test different product criteria for extended periods, such as the softgel’s ability to dissolve or disintegrate. If crosslinking has occurred in this time frame, it will be obvious to the formulator when the product samples are removed from storage and tested.
When crosslinking occurs, this usually becomes evident at the end of a project. It’s a challenge because a sponsor company might invest significant resources into a fill formulation and then realise that they’ll have to start over again and reformulate their product. Certain chemicals have been identified that cause crosslinking issues with gelatin. And, in situations when one of these is present, it would be advisable to begin formulation with a product that has a higher suitability to the type of critical formulation.
This is when StabiCaps comes into play. Our research has helped us to develop a testing protocol to predict the behaviour of gelatin in the presence of crosslinkers. Already, the predictive test has proven to be a major step forward in our understanding of this field.
Pierre Albert Thomas, Rousselot’s Global Director of Functional Ingredients
Pierre Albert Thomas, Rousselot’s Global Director of Functional Ingredients
AKA: How does StabiCaps overcome the issue of crosslinking?
PAT: When discussing crosslinking, there are a few drivers that influence the phenomenon. There are, of course, some external factors that we can’t control, such as the environment. However, there are intrinsic characteristics of gelatin, such as its molecular weight, that can affect a softgel’s
stability.
Generally speaking, gelatin is highly standardised to minimise batch-to-batch variability. This involves blending different semifinished gelatin products to assess their impact on the characteristics of a particular product. One of the important aspects to consider is the molecular weight. Often, the molecular weight of a gelatin used to make softgels is selected from a manufacturing or productivity standpoint, rather than stability.
The key in Rousselot’s StabiCaps solution is the focus also on the softgel’s stability, with a molecular weight that is suitable to limit its
crosslinking potential.
AKA: Will there be any equipment, process or regulatory changes required to include StabiCaps in existing formulations?
PAT: From a regulatory standpoint, there are no regulatory impacts associated with StabiCaps; this solution is true gelatin, which meets all the requirements of the International Pharmacopoeia. There will, no doubt, be marginal changes to the manufacturing process; but no special equipment
should be required as StabiCaps is intended to operate efficiently on a regular encapsulation machine at a comparable speed.
In terms of formulation, there may be some necessary adjustments owing to the gelatin’s specific molecular weight. This impacts the rheology of the gelatin, so this must be accounted for during the formulation stage.
We also have guidelines for our customers to take them in the right direction. In our application lab, we can work on a given formulation, so that, once the customer decides to use StabiCaps, they will have a defined starting point they can use for that specific product. We’re not talking about drastic
changes, here, but only slight adaptations.
AKA: Does StabiCaps have any effect on fill release?
PAT: StabiCaps does indeed affect fill release, but in a positive way; this is because it overcomes the stability issues mentioned above. In terms of how it might interact with a specific API, because StabiCaps is regular gelatin, there aren’t any issues.
In addition, by testing the solution in an industrial setting we discovered that there are further advantages to utilising StabiCaps. Besides improving the crosslinking behaviour, we noticed that the maturation time of the gel mass was reduced, which is interesting from a productivity standpoint. The product also dries more easily. While these benefits weren’t initially at the core of our design goals for the solution, they are certainly welcomed enhancements.
AKA: What sets StabiCaps apart from your competitors?
PAT: StabiCaps is one of the few currently available solutions to address crosslinking issues at a commercial level. If we were to compare alternative products within the same market segment, one advantage of StabiCaps is that it uses real gelatine — not one that’s been altered with the addition
of other ingredients.
The Rousselot offering comprises a true, standardised gelatin with an adapted molecular weight that offers the same high-throughput production rates as traditional gelatin. This means that there will be no issues with stickiness or lower productivity that might occur with other solutions. Adding something to the gelatin can alter its behaviour, so that’s why we kept it pure. From a regulatory and production point of view, StabiCaps is a gelatin, and works as such, with only marginal formulation changes.
Additionally, the fact that we offer testing services to help prevent crosslinking occurring sets us apart from our competitors. The combination of our product and the technical support we offer customers, such as the formulation guidelines and stability trials,
makes StabiCaps a holistic solution for any softgel manufacturer.
