Customized fill release for soft caps
GELITA offers numerous types of pharmaceutical gelatin that enable a fill release at the right time and in the right place
Gelatin capsules are among the most popular dosage forms for pharmaceutical applications, over-the-counter (OTC) products and dietary supplements. And with good reason: Thanks to their smooth surface, they are easy to swallow and thus facilitate regular intake of certain active ingredients and nutrients. Also, gelatin is non-allergenic and consists of proteins that are easily digested in the gastrointestinal tract. However, when a delayed release is desired – which is critical for some substances – or capsules are exposed to difficult storage conditions, there is a limit to what the conventional pharmaceutical gelatin can achieve. That’s why GELITA has developed some very specific variants that give capsule manufacturers full control over the release of active ingredients.
Release control
Although there are many different kinds of substances provided in capsules, not every capsule type is suitable for every kind of fill. For example, for liquids or pasty substances soft gels are usually the first choice, while granules or powders are mostly delivered in hard capsules. Compared to solid fillings, liquids have the advantage of being easier to digest. This can improve the bioavailability of ingredients or even the absorption of poorly soluble drugs. Soft capsules are particularly well suited to sensitive ingredients because they provide protection from oxygen, light, contamination and microbial growth. Unlike other types of capsules, they are hermetically sealed, masking any unpleasant taste or odor of their contents – at least until they reach the stomach. Because it is here that conventional gelatin capsules dissolve in the aggressive stomach acid.
Controlling the release of the capsule contents is important for two reasons: Firstly, it makes it possible to define precisely where in the body the active ingredient or nutrient should be released. Secondly, the speed of the release can be determined. Take painkillers, for example. Here, it’s important that the ingredients are released as fast as possible to provide the consumer with quick pain relief. With dietary supplements such as fish oil capsules, however, the opposite may be required. In this case, the fill shouldn’t be released in the stomach in order to prevent a distinct fishy aftertaste familiar to almost anyone who has ever consumed fish oil. That’s because, if fish oil is released in the stomach, it floats to the top and can cause some fishy burps. Therefore, many manufacturers have tried to make their capsules enteric (resistant to aggressive stomach acid) to ensure a delayed release in the intestine. Most of them rely on a capsule coating that is added during an extra production step. This, however, results in an additional production step causing extra time and extra costs, too. The coating can also lead to an opaque shell around the capsule that makes it less visually appealing.
To solve these problems, GELITA has developed the pharmaceutical gelatin product GELITA® EC. It enables the production of enteric capsules that only dissolve in the small intestine rather than the stomach. With GELITA® EC, visually appealing enteric capsules can be produced in a one-step process – using existing equipment – that also comply with all relevant Pharmacopeia dissolution parameters.
Reduced cross-linking
Certain reactive fills or extreme storage conditions – such as high temperatures and high humidity – can cause the gelatin to react and crosslink. As a result, soft capsules can become less soluble over time. It can then take longer for them to dissolve which may result in a delayed release of the fill.
With GELITA® RXL, GELITA has developed a natural solution, consisting of 100% gelatin. This special gelatin significantly reduces cross-linking and thus improves the dissolution properties of soft capsules. Various attempts by the pharmaceutical industry to reduce cross-linking with the use of certain additives have been only partially successful. That’s why GELITA has taken a different approach, and developed a new manufacturing process that controls molecular weight distribution. The GELITA solution can be described as a kind of “self-defense mechanism” based on a combination of large and small molecules. These molecules react with each other to prevent gelatin cross- linking and/or undesirable reactions with the capsule contents.
Fast delivery
When it comes to products such as painkillers or cough and cold remedies, consumers want immediate relief. To accelerate the dissolution of the capsule and speed-up the fill release, e.g. in analgesics, GELITA has further developed the RXL concept and launched GELITA RXL R², a capsule gelatin providing “revolutionary fill release” performance, with an up to three times faster fill release compared to conventional soft caps.
In cooperation with the University of Heidelberg, GELITA tested this formulation and analyzed the advantages of soft capsules containing GELITA® RXL R2. For this purpose, the capsules were stored for up to twelve months under various ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) storage conditions. A standard pharmaceutical gelatin and GELITA® RXL served as comparison.
To check the stability of the capsules, they were stored in closed glass vials at 22°C/50% relative humidity (RH) and at 30°C/65% RH for a period of twelve months each, and at 40°C/ 75% RH for a period of six months. The dissolution behavior of the capsules and the release of the fillings were monitored in simulated gastric acid at 37°C. In addition, the molecular weight distribution of gelatin in the capsule shell was determined by gel permeation chromatography (GPC).
The results show that fresh RXL R2 soft capsules dissolve most rapidly at pH 1.3. After six minutes, they had already released more than 70% of the fill. Even after a storage period of twelve months at 22°C/50% RH, this rapid initial release remained constant. The release rates of standard RXL capsules were somewhat lower (Figure 1).
However, the real performance of GELITA® RXL R2 capsules was demonstrated during the accelerated ICH storage test. At neither 30°C/ 65% RH nor 40°C/75% RH could the scientists detect any change in the dissolution and release profile (Figures 2 and 3). However, it was a different story for the conventional gelatin soft capsules: Compared to the GELITA® RXL R2 capsules, these took almost three times as long to release 50% of their fill.
Martin Junginger, Head of Global Product Management Pharma at GELITA, comments: “These results prove that the performance of our RXL R2 capsules is maintained even in extreme conditions. Whether fresh from the factory or after a year of storage in harsh conditions, manufacturers can be confident that their active ingredients or nutrients will be released exactly as desired.”
An experienced partner
With its broad portfolio of pharmaceutical gelatins, GELITA offers solutions that comply with all existing regulations while meeting virtually every conceivable requirement. In the search for the appropriate gelatin for different applications, GELITA’s experts are happy to support customers with in-depth knowledge and technical service. This not only speeds up product development, but also reduces the risk that a capsule formulation, once developed, will not meet dissolution or storage requirements, or consumer expectations.
