Summary:
Gelatine capsules are among the most popular single unit dosage forms for drugs (Rx), over-the-counter (OTC) products and food supplements. While hard gelatine capsules are primarily used for powder applications, soft gelatine capsules are the preferred dosage form for liquid, paste-like or oil-based active ingredients. In general, soft shell capsules release their contents within a few minutes. However, certain types of reactive fillings and extreme storage conditions — such as high temperatures and humidity — may cause the gelatine in the capsule to cross-link and harden. This can result in longer dissolution times in the GI tract and in the slower release of active ingredients. To prevent cross-linking, even under the longest and harshest ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) storage conditions, GELITA has recently introduced GELITA® RXL R2 gelatine, the next generation of its GELITA® RXL product.
Overview:
The fast and reliable release of active ingredients is becoming increasingly important. Survey data from Datamonitor1 suggest that, worldwide, more than 50% of consumers want “fast and effective” results for immediate relief. They also state that claims such as “results achieved quickly” play an influential role regarding their opinion of a health or beauty product. Especially manufacturers of analgesics and cough/cold products have tapped into this trend: these categories comprise 40% of new launches tagged with speed and efficacy claims.
The manufacturers’ challenge is to make sure that their products deliver reliable effectiveness and speed of performance, irrespective of external conditions. Hence, the risk of gelatine cross-linking could present problems to the capsule industry. Capsules that perform normally when freshly made can gradually become less soluble during shelf life. When cross-linking occurs, a thin, less water-soluble layer is formed at the interface of the capsule shell and the filling. Gelatine’s tendency to cross-link can adversely affect the long-term stability of certain capsule products and, in turn, hinder logistics and, ultimately, profitability.
Cross-linking is strongly influenced by the presence of aldehydes or ingredients in the fill formulation which have a potential to crosslink with gelatine; yet, testing indicates that the process that renders capsules less soluble can also happen when they’re stored at elevated temperatures and humidity levels for a very long time, even in the absence of aldehydes. Indeed, some reactive medicines cannot be formulated into standard gelatine capsules because the final product is unable to pass the required storage tests. As a result, normal quality control procedures often include shelf-life and accelerated longevity testing as part of the qualification and surveillance protocols to ensure efficacy for the product’s entire lifetime.
Various attempts by the pharmaceutical industry to reduce cross-linking with additives have only been partially successful. GELITA, however, followed another route: They developed a manufacturing process with a defined and precise molecular size distribution of the RXL R² gelatine. Small, highly mobile gelatine molecules are, under suitable conditions, able to block the cross-linking effects of the larger gelatine molecules — similar to interfering with the interaction between a key and its lock.
GELITA offers various grades of pharmaceutical gelatine that fit the individual requirements of the manufacturer. The latest development of their Pharmaceutical Competence Team is GELITA® RXL R2 that takes the reduced cross-linking (RXL) concept provided by GELITA® RXL one step further and brings rapid release (R²) performance to the market.
