Pharma’s going soft: Looking at the growth of soft gels and their benefits to pharma

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Soft gels have seen huge growth in the pharmaceutical industry in recent years thanks to versatility and convenience, here, Pierre-Albert Thomas, global technical support manager, Rousselot, discusses this trend and how soft gels can benefit the sector.

While relatively new to the pharmaceutical industry, soft gels have seen huge growth in recent years. They hold universal appeal to consumers and manufacturers alike, thanks to their versatility and convenience.

Soft gels’ unique functional benefits provide extended shelf life and stability of active pharmaceutical ingredients (APIs), as well as allowing accurate dosing and optimal delivery. As they are easier to swallow than other formats, such as tablets in particular, soft gels are a popular choice with consumers.

Manufacturers are now turning to gelatine soft gels to meet the rising demand for clean label nutraceutical and pharmaceutical products. As the main excipient in the capsule market that offers pharmaceutical grade standards and a high degree of stability, gelatine also provides additional reassurance in the delivery of more complex and sensitive compounds.

Rising popularity

The popularity of soft gel capsules shows a clear increase — it is predicted that the global market for such applications will grow at a CAGR of 5.4% over the next decade, reaching an estimated $316.6 billion by 2025.1

This growth has been driven by innovation in capsule formulation, as well as the high consumption of supplements and pharmaceuticals — it is estimated that nearly half of all adults (50% of women and 43% of men) in the UK now take prescription drugs.2

To meet the rising requirements of consumers, new formulations are constantly being developed, to accommodate specific fills. The market is changing; 90% of recently developed APIs have low solubility, creating a range of formulation challenges.3

Soft gel capsules are a viable option, as they can carry dispersions, emulsions or self-emulsifying systems, which improve the absorption of poorly soluble nutrients. Manufacturers are therefore looking at different gelatine types, to optimise the delivery of APIs to the body.

A trusted choice

Gelatine is widely used as the preferred excipient in soft gels — and has a longstanding heritage in capsules of over 100 years. This is because it meets stringent pharmaceutical regulatory requirements, and has robust functionality and full compatibility with the human body.

A fully digestible, natural protein extracted from collagen found in the skin, bones and connective tissues of animals, gelatine is regarded as a safe and natural excipient. It is extensively used in many pharmaceutical applications, thanks to its functional benefits, such as film forming, thermo-reversibility and rapid absorption.

Optimising gelatine for API delivery

Despite its advantages, formulating and manufacturing soft gel capsules to fulfil the latest specifications and end-use requirements can be complex and challenging. As different grades of gelatine can be selected to produce soft gels, there can be different rates of stability and dissolution, which affect the delivery of APIs to the body. As such, soft gels are being developed to work with specific delivery systems, such as delayed release or chewable capsules.

There are several factors that impact delivery of the active ingredient, including the speed of dissolution of both shell and fill, as well as its gastro-resistance. A key requirement of soft gel capsules is to protect against early degradation while in storage. However, they are particularly sensitive to heat and moisture, affecting the shelf-life stability. To counteract this, a high-quality gelatine should be used, and all steps of the process strictly controlled, such as the drying stage, to achieve suitable moisture. An internal study performed in 2013 on fish oil formulations showed that soft gels moisture levels of below 11% help avoid instability and subsequently, a sticky texture.4

The correct choice and combination of gelatine and processing conditions can help retain shell inertness in soft gel capsules. This is important in such dynamic systems, as components may move between shell and fill, as well as from the external environment into the shell. Capsules are then at risk of becoming unstable and brittle, as different components to react together. Shells can also lose their shape, softening and lowering the level of protection available for APIs. Without adequate protection, the likelihood of oxidation and recrystallisation increases, lowering the overall effectiveness of the capsule.

Choosing a compatible gelatine can help to prevent crosslinking — the undesirable formation of strong chemical linkages between gelatine chains. Capsule shells can become tough, rubbery and insoluble, causing soft gel instability and lowering the API delivery rate to the body. Research has shown that some parameters, including gelatine molecular weight distribution, may impact the ability of gelatine to crosslink. In response, Rousselot has developed a protocol to predict how gelatine will behave under adverse conditions. Being able to accurately assess the crosslinking behaviour of different gelatine types allows the pharmaceutical industry to choose the right type for their soft gel capsules. As tailored gelatines become recognised for their ability to prevent crosslinking and instability, they are increasingly being used by manufacturers to create innovative customised solutions.

All gelatines are not equal

For soft gel manufacturers, it is important to choose the right high-quality gelatine that can provide the necessary benefits, without any of the typical defects, such as poor encapsulation yield, twins and leakages. When formulating soft gel capsules, not only is it important to prepare a gel mass that displays consistent high quality, it also needs to display minimal foaming and enable perfect films, to maintain high production efficiency. To ensure optimum manufacturing and API delivery to the body, gelatine must also be highly soluble, easy to use and exhibit excellent mechanical strength.

Rousselot has developed safe, non-allergenic and fully compatible pharma gelatines that help to meet the needs of manufacturers, both for hard capsules and soft gels. Compliant with safety, quality standards and practices, like IFS, HACCP and GMP, the range of gelatines can help to minimise risk of soft gel defects during manufacture, maximise productivity throughout the formulation process, and save costs. Offering certified Halal and Kosher gelatine options also provides additional appeal to consumers with religious requirements.

Continuing to innovate

Ensuring optimum API delivery with the use of soft gel capsules can be a challenging process for pharmaceutical manufacturers. Complex production methods, coupled with increasingly stringent industry regulations means that choosing the right type of gelatine is fundamental to achieving optimum soft gel capsules.

As such, it is important to pay close attention to the specific properties of gelatine and benefits they confer, including absence of crosslinking and increased bioavailability, to ensure a smooth and efficient manufacturing process of pharmaceutical soft gels.

References:

  1. Research and Markets, 2016, Softgel Capsules Market Analysis & Trends — Application (Health supplement, Vitamins & Dietary Supplements, Cardiovascular Drugs, Anti-Inflammatory Drugs and Antibiotic & Antibacterial Drugs), End-User — Forecast to 2025.
  2. The Health Survey for England 2013.
  3. Kalepu, S., and Nekkanti, V., Acta Pharmaceutica Sinica B, 2015;5(5):442–45
  4. Internal Rousselot study, Ghent Application Lab, 2016.
  5. Global Industry Analysts Inc., Gelatin, A Global Strategic Business report, Nov 2016.