Omega-3 long-chain polyunsaturated fatty acids such as docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and alpha-linolenic acid (ALA) are very popular within the dietary supplement sector for their ability to help maintain normal heart function (EPA and DHA), normal blood cholesterol levels (ALA), and eye and brain health benefits (DHA). However, the propensity of omega-3 oils to turn rancid and develop a characteristic fishy smell and taste may negatively impact consumer appeal.

The cause of this instability is due to the molecular structure of the oils, and the high double bond content within them. EPA and DHA contain more double bonds than ALA and so are at higher risk of degradation. Water content can also have an impact. The quality of the oil can be measured by testing its anisidine and peroxide values to determine the number of double bonds that remain.

Omega-3 oils are predominantly marine-based, sourced from fish, Antarctic krill, and green lipped mussels. Even seal oil is a source of EPA, DHA, and docosapentaenoic acid (DPA). Biotechnology is being harnessed in the hunt for plant-derived sources of EPA and DHA. For example, yeast can be engineered to produce EPA. Microalgae also offer a source for omega-3s and are the ultimate source of the EPA and DHA found in fish, as they are part of the fish’s food chain.

Fish oils were traditionally served as liquids, with consumers taking a spoonful a day. However, the associated taste, and propensity for reflux giving an unpleasant aftertaste, made those products off-putting for many. The taste would often be described as rancid, which is caused by the natural oxidation of the molecules, which may be accelerated by the presence of trace metals or enzymes within the oil.

Minimizing the levels of impurities within the oil alone cannot stop the degradation of products caused by exposure to atmospheric oxygen. Serving the product on a spoon exposes the bottle’s contents to oxygen as soon as the seal is broken for the first time, so alternative formulations, to increase both the shelf life of products and consumer appeal, is desirable. Encapsulation of products into softgel capsules not only prevents the degenerative process, but can also use advanced formulation techniques to disguise their tastes (or aftertastes). This has made the consumption of omega-3 supplements a much more pleasant experience.

Manufacturing Optimized Products
Whatever the source of the omega-3 oils, be it marine or plant-based, it is paramount to have the highest quality oil for an optimized final product. Once the source is determined, an optimal antioxidant accounting for the variation between omega-3 batches and source needs to be determined.

Antioxidants can be formulated into products alongside oils, scavenging the free radical molecules brought about during the oxidation process. Tocopherols are naturally present in some sources of omega-3 oils and are commonly used in supplements as antioxidants. Other compatible antioxidants include citric and ascorbic acids and a range of spice extracts. Commonly, blends of antioxidants are employed, as they can have synergistic effects, but there is no single solution that works with all oil ingredients and all product formats. The optimal antioxidant will depend on a variety of factors and needs to be selected with care. Storage and handling of the bulk oils throughout the manufacturing process under a blanket of inert gas such as nitrogen or argon can help minimize oxidation.

Processing needs to be undertaken in a closed system purged with an inert atmosphere to ensure all handling and transfer of bulk oil does not expose it to the risks of atmospheric oxidation.

In addition to oxidation, omega-3 oils are prone to degradation brought about by exposure to heat and light, so manufacturing must be carried out with care. Proper storage and handling must be employed at all times to maintain product quality.

For over 80 years, softgels have been an ideal dosage form for omega-3 oils. Softgels are liquid filled soft capsules that are produced using the rotary-die encapsulation process invented by Robert Pauli Scherer in the 1930s. The shells are typically comprised of gelatin, water, and plasticizers such as glycerin or sorbitol. They can also include colors, opacifiers, and flavors to give specific effects and distinctive market properties. Advances in formulation technologies have led to the development of non-animal derived shell material for vegetarian alternatives. One of the most prominently utilized is the seaweed-derived hydrocolloid iota carrageenan in combination with starch. Softgels using vegetarian materials for encapsulation are becoming increasingly popular to meet consumers’ dietary requirements.

Softgel capsules dominate the omega-3 oil supplement market as the encapsulation procedure is very compatible with the oil, and consumers have become very comfortable with the format. The products are convenient, have a long shelf life, and are not as messy as bottles of liquids.

The shell is formed from two ribbons of a gel, which need to be thick enough to provide a barrier to oxygen permeability, yet not so thick as to be excessively costly in materials or become difficult to work with. These ribbons are made in-situ and then brought together between two rotating dies with capsule-shaped indentations. The liquid fill is then injected between the ribbons and the capsules are then sealed to form the final product.

The final step of the manufacture is the packaging of the individual softgels into bottles or filling into blister packs. Despite the softgel coating providing enhanced protection from atmospheric oxidation, it is preferable that this is carried out under an inert atmosphere. For total quality control, stability tests should be conducted on the final product to ensure the processing steps have not adversely impacted the quality of the omega-3 oil.

Innovative Omega-3 Dose Forms
In the highly competitive market of dietary supplements, new innovations around dosage forms can increase the appeal of products among consumers. Dose forms that do not require water, such as chewable capsules, have large consumer appeal in general and especially for populations that have trouble swallowing, such as the elderly and young children. Formulations allowing for the development of such a product would require more concentrated fish oil ingredients and suitable taste masking additives, and could afford a step change for the specific market, similar to when softgels were introduced, replacing liquid dosing.

Enteric coated softgels can potentially create a product with a modified delivery profile and allow the dissolving of the capsule to be controlled within the gastrointestinal tract. By introducing an acid-stable coating, the capsules will pass through the acidic conditions of the stomach and then dissolve in the more alkaline conditions of the small intestine, which reduces reflux and minimizes the potential for unpleasant, fishy aftertastes.

The health benefits of omega-3 supplements means the market for products remains strong. Creating products with consumer benefits can lead to success, but above all, quality is paramount. For manufacturers, it is crucial that sourcing of omega-3s, the processing, handling, and packaging of the final dose all be carried out carefully and precisely, to ensure consumers receive the optimal product every time.