The softgel revolution

Improved dosage forms for ageing populations

The global market for consumer healthcare products is enormous, with Euromonitor putting total sales at more than $210 billion in 2015. Their estimates claim that this is set to increase by 16% by 2020.1 Various product categories are rising steadily, such as over-the-counter (OTC) oral painkillers which, according to the same source, represented a $21 billion market in the same year and is expected to increase more than 11% by 2020.

Many OTC products are particularly appropriate for older consumers in this expanding market, as they address conditions that become more prevalent with age. The range of available products is expanding too, with ever more prescription medicines that are aimed at conditions affecting the elderly making the switch to OTC.

Yet, the consumer healthcare market is an intensely competitive one. No single company had a value share of more than 5% of the global consumer health market in 2015.1 It is therefore important for manufacturers to create differentiated products, with perceptible advantages for consumers that will encourage investment in their products rather than those of the competition.

Consumer health products that are available in easy-to-take dosage forms are likely to outshine those that are less convenient; and, with convenience, comes improved compliance. For example, painkillers that act more rapidly may well be considered worth the premium price compared with a standard formulation.

The softgel capsule is already very popular with consumers, and some products in the consumer healthcare market are rarely seen in any other form than a softgel. They are easy to swallow, and recent formulation advances have enabled the creation of rapid onset versions and pleasant-tasting chewable forms.

Fills can be modified to reduce reflux odour in products such as fish oils and garlic supplements, and enteric coatings can be added to give better control of where the active ingredient is delivered in the gastrointestinal tract. The appearance of the product can be tailored too, and a choice of colours, opacity and inline printing can be used to decorate the capsules, perhaps to make them more appealing to children or to increase brand recall and differentiation.

The introduction of the rotary die production technique by Robert Pauli Scherer, which helped softgel capsule manufacturing to transition from a bespoke manual ‘craft’ undertaken in pharmacies to a highly controlled automated manufacturing process, came more than 80 years ago in the 1930s. The ingredients in a standard softgel shell include gelatin, water and plasticizer ingredients such as sorbitol or glycerine. Opacifiers and colouring ingredients are commonly incorporated to make the products more attractive, and to help protect fill ingredients that are sensitive to light degradation. Flavours may also be added to improve the palatability.

The active ingredient inside the shell is present either in solution, dissolved in an oil or polyethylene glycol, or as a powder suspension in oil. The shell plays an important role in providing protection from the environment, which, as well as protection from light, is important for ingredients such as fish oils that are susceptible to oxidation when in contact with atmospheric oxygen, or hydrolysis in the presence of water.

Recent developments include the replacement of animal-derived gelatins with plant polysaccharides. This permits the creation of softgels that are appropriate for a vegetarian diet and serves the needs of certain religious groups, expanding the dosage form’s market appeal to a wider population of consumers.

OTC formulation choices

If the drug’s active ingredient has good bioavailability, then a simple softgel formulation in suspension, solution or emulsion may suffice. For those with poor solubility but good permeability, a more creative lipid-based delivery system is more likely to be successful. The compositions of lipid-based formulations can vary from 100% oil right down to oil-free, with the addition of hydrophilic or lipid-based surfactants, or a hydrophilic cosolvent. This wide spectrum of options allows for great flexibility in the quantity of active ingredient that the softgel can contain.

If the formulation is mainly oil, then digestion will almost certainly be required for absorption to occur. In contrast, a self-emulsifying lipid-based system is designed to disperse and form a microemulsion on contact with water, with no digestion required. Self-emulsifying drug delivery systems (SEDDS) can play a key role in reducing inter-patient variability, which is an increasing problem for more elderly consumers.

Bioavailability improvements

Softgels can frequently give faster absorption rates than traditional tablets. If the active ingredient is in solution form within the softgel, this can often lead to better bioavailability and higher levels of the drug reaching the bloodstream. Similarly, a self-emulsifying system that contains suitable surfactants can have this effect. Improved bioavailability may also result in lower doses being required.

This effect can, in certain cases, even be achieved if the softgel contains a suspension, as opposed to a solution. If the active is milled into submicron particles and then incorporated into a lipid-based formulation, it may be more likely to dissolve in the gastrointestinal fluid. Again, this will have the effect of increasing bioavailability compared with a more traditional tablet or capsule.

The softgel is also a particularly appropriate format for products with very low dose levels — because the product can be accurately dispersed into a larger volume of liquid. Vitamin D is a good example, as the recommended daily allowance (RDA) for adults is 15µg in the US and just 5µg in Europe. With such low doses, uniformity from one dose to the next is simpler to achieve with a softgel than a traditional compressed tablet or hard-shell capsule.

Novel softgel products

The polysaccharide-based capsules that have been developed in recent years have additional advantages over and above their avoidance of animal-derived gelatins. The gel material is compatible with higher processing temperatures, extending the range of ingredients that can be formulated and allowing a more concentrated film to be created, giving smaller capsule sizes. It is now possible to make even smaller softgel-based products thanks to recent innovations in manufacturing technology. Mini softgels or tiny beads measuring 2.5–4.5mm in diameter and packed into sachets have proved to be incredibly popular for fish oils in the Japanese market.

The process used to make them, OptiGel Micro technology, employs a pair of concentric tubes with the central tube containing the fill, and the liquid gel being fed through the outer tube. Both materials are then dripped simultaneously into flowing oil, which causes the formation of the tiny, regularly sized, softgel beads. Although the technology has yet to be commercialised more widely than the Japanese fish oil market, the potential of these miniaturised softgels is enormous.

They are even easier for elderly patients to swallow as they are so small, and the process is compatible with both animal-derived gelatin and its polysaccharide replacements. Enteric coatings can also be applied to delay release of the softgels’ contents. The coating principle leads to the intriguing possibility that two different actives can be incorporated within a single softgel product, one in the fill and a second, low-dose active ingredient in the coating.

This is particularly attractive for the more often heavily medicated geriatric market as it may help to reduce the number of drug products, sometimes referred to as the ‘pill burden,’ that the consumer has to remember to take. SoftDrop oral technology can also include two actives, one in the fill and the second in the shell.

Another product type likely to be particularly suitable for ageing consumers — and also for children — is the chewable softgel. They are designed to disintegrate in the mouth and release the active there, so they do not need to be swallowed. This also means they are suitable for people who may have difficulty swallowing.

The manufacturing process for chewable products has improved greatly during the past few years, with products such as Catalent’s EasyBurst chewable technology entering the field. This uses a thinner gelatin shell than is found in a normal softgel, which allows it to break easily on chewing. The result is a product that disperses in the mouth and is simple to swallow without water. They are more challenging to make than regular softgels, but when combined with careful taste-masking technologies, the result is a product format that could provide significant product differentiation on the pharmacy shelves.

Although softgel technology dates back decades, it has remained far from static. Since they first appeared, they have gained significant acceptance from consumers and, according to market analysts, more than 80% of consumers consider them to be easy to swallow.2 Many formulation developments and improvements have been made in recent years, with the aim of distinguishing products in an increasingly crowded market space. It is important that innovators and developers continue to make strides in product performance, and keep consumers in mind when they do so.

The ageing population is targeted by many market sectors, not least for the specific demands and challenges it brings, and the use of softgels as a dosage form is just one example. Softgels are not a new concept; indeed, they have been available for more than 80 years, but the innovative development of the technology, such as rapid onset, increased palatability and the ability to tailor both appearance and flavour characteristics have all been made in recent years to adapt to changing market needs and consumer demands.

Innovators are seeing where advantages in prescription medicines or consumer health can be transposed to benefit particular patient groups to improve the commercial appeal of products, and the marketplace will continue to evolve to meet the demands of the real beneficiaries, the consumer.

References

1. Euromonitor International: http://blog.euromonitor.com/2015/12/consumer-health-an-end-of-year-review-of-2015-performance-to-advance-market-strategy-in-2016-and-beyond.html (2015).

2. Marketing Analysts LLC, OTC/VMS Delivery Forms Study (2009).

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