Developing Vegetarian Softgels

For oils or many poorly absorbed drug products, softgels are an ideal dosage form. The only oral dosage form (excluding liquid-filled hard-shell capsules) able to contain a nonaqueous liquid hermetically, softgels also offer substantial flexibility, due to the numerous sizes and shapes available.

The outer shell portion in most softgels is made from gelatin, an animal product derived from one of several sources: bovine (beef), porcine (pork) and piscine (fish). For many formulations, the softgel is either the only possible dosage form or the ideal preferred one. Unfortunately, this dosage form can be an issue for some people because, whether for religious, cultural or personal preferences, the ingestion of animal or specific animal products is unacceptable. The concern over bovine spongiform encephalopathy (BSE) with beef gelatin, which, in reality, is quite unlikely, also worries some consumers. Thus, non-animal or vegetarian softgels have a position in the marketplace.

Gelatin is a tough item to replace, especially in softgels. Gelatin is comprised of nearly 90 percent protein. It is well-known that colloidal gels for oral use can be made with many other substances: starches, gums, celluloses, collagens, etc.; but, most of these compounds are not strong enough to work or function as needed in a softgel capsule. In fact, there are very few substitutes that exist for a bio-polymer that are as strong and tough as gelatin, and can be ingested. Notably for softgel use, the gel used must be thermally reversible (meaning it can exist in a liquid state under heat and in a solid state at room temperature) in order to work on a softgel encapsulation machine and still be able to melt at body temperature.

The recent status of non-animal or vegetarian commercially produced softgels has been with utilizing starches or carrageenan-starch blends to make the shell. Numerous formulation and/or ingredient patent applications have been filed in this area. Until recently, there were a few significant drawbacks in using these kinds of softgels compared to normal gelatin. The first is shell brittleness, resulting in some fragility (easily breaking open and leaking) of the softgel. The second is a size/fill limitation (normally not more than a 12 oval), a result of inherent brittleness—the larger the softgel, the more apparent the problem. Third, there are some possible incompatibilities between the fill ingredients and the shell materials, resulting in softgel failure. This is more likely to occur when powdered ingredients are added to the oil-based fill material (what insiders call “paste” products). Softgels made utilizing carrageenans are a bit stronger than those made simply with starch.

Carrageenan comes from seaweed (vegetarian) and has been widely used in the food industry for many years as a thickening and stabilizing agent. Carrageenan is not a singular substance, but a compound made up of several different polysaccharide chains, each of which has different characteristics and is sold and named commercially as iota, kappa or lambda. Iota is soft. Kappa is strong and rigid.

Lambda forms a gel only when mixed with protein; it is not used for softgels. Two softgel companies have already patented the use of blending iota and kappa carrageenans together with starch for making softgels.

The latest major innovative ingredient is a new form of carrageen called Sea Gel™, manufactured by FMC Biotechnology, a large pharmaceutical excipient company and a major carrageenan supplier. As such, they located another new carrageenan polysaccharide called kappa2. FMC patented the use of this ingredient and its related technology in the manufacturing of softgels. What is unique about this material is it is a single polysaccharide chain that naturally contains both iota and kappa carrageenans. This means not having to blend the two polysaccharides together, naturally delivering both strength and flexibility. The significance of this material is that the softgels produced are also strong and pliable. No brittleness issues means all normal softgel sizes can be produced, even 20 oblongs (the size used in 1,000 mg fish oil softgels). This is a major improvement and advance in the making vegetarian softgels.

This non-animal softgel technology is currently available for mass production. Although work still continues in improving non-animal or vegetarian softgels, there is a viable non-animal option that many companies can consider.

Robin Koon is senior vice president of Best Formulations (BestFormulations.com). Best Formulations is one of two licensees of FMC’s patented SeaGel technology.