Nutraceuticals: Why Consumer Demand for the Softgel Sector is Growing and How Form and Formulation are Driving Innovation to Combat Pill Fatigue

Pill fatigue is a real phenomenon that is shaping consumer choice regarding the nutraceuticals millions of people voluntarily prescribe themselves every day. Pill fatigue has many sources, but it primarily has to do with dose adherence or compliance and is attributable to the challenges people face by the number, size and frequency of the pills they take.¹ Although tablets and capsules will always have their place in the medicine cabinet, a 2015 survey of people across the United States and Germany by the Spiegel Institut revealed that half of the population had difficulty in swallowing tablets and capsules.² According to the study’s 1000 US respondents, swallowing problems were attributed primarily to the size of the tablets and capsules – either being too big to swallow or that they became stuck in the throat. 

The study, commissioned by prominent over-the-counter (OTC) drug developer Hermes Pharma, found a full 10% stopped taking their medication entirely, while 9% looked to a different dosage form altogether. According to Spiegel Institut’s data over half of the US participants (66%) reported that to aid compliance dose forms should be easy and comfortable to swallow, 38% said that a pleasant taste or odor was important, and 34% wanted a product that integrates easily into their lives.² 

Form, Function, and Efficacy in One Attractive Dose 

For most of nutraceutical development and drug commercialization history, oral solid dose (OSD) forms have dominated. Most nutritional extracts, botanicals, minerals, vitamins, and other compounds have been traditionally either encapsulated or pressed into tablets. As pharmaceutical and material science advanced during the early 20th century a new OSD form emerged, the softgel. Since then, softgels have become one of the most popular means to deliver a vast array of supplemental and nutraceutical formulations and a trend that has only seen to be accelerating post-pandemic.

The momentum and potential of the market has many prominent food and pharmaceutical companies investing considerable financial and organizational resources to reach these consumers. There is tremendous opportunity ahead, with industry analysts projecting the global nutraceuticals market to grow from the approximately $350B it is today to approximately $650B by 2030.^3,4 

Consumer preference for softgel capsule technology to deliver pharmaceutical and nutraceutical products is gaining momentum and generating tremendous opportunity for product developers—primarily due to their patient-centric form. Softgels’ luster also imbues quality and efficacy, and most people perceive them as easier to swallow. The consensus among analysts is that increasing awareness of health supplements in general, the growing number of nutraceutical and softgel manufacturers in the market, and a distinct surge in product sales during and post-pandemic, are all driving the market for softgels to unprecedented levels. 

Valued at approximately $8B in 2022, the global market for softgel capsules is estimated to reach $13B by 2030 at a robust compound annual growth rate (CAGR) of 7.9%. Although the total industry figure frames the massive market for softgels, nutraceutical and cosmeceutical companies dominate and represent the largest revenue-generating market segment for the technology.⁵ 

Consumers want their nutraceuticals to possess these five things in order: taste, health benefits, be free from additives, environmentally friendly and non-GMO. They also want them to be easy to swallow and affordable. One look down any ‘Nutrition & Supplements’ aisle in any grocery store or pharmacy will confirm just how popular and successful softgels have become in delivering medicines and therapeutic substances to a broad range of consumers.

Softgel’s Unique Value Proposition 

Softgel capsules are unique in the way they increase the efficiency and effectiveness of active ingredient delivery. The current softgel manufacturing process was pioneered by Robert Pauli Scherer in 1932.⁶ Incorporating a rotary die mechanism, softgel encapsulation is essentially a single formfill-seal process. Because softgels are a universally preferred OSD form, product developers are increasingly recognizing their value in delivering active nutraceutical ingredients and formulations. Softgels provide a versatile OSD vehicle for liquid, semi-solid suspensions and hard-to-handle powder APIs that can’t be pressed into tablets. 

Advancements and refinements to manufacturing technology and the emergence of alternative shell formulations have added even more utility to the dose form. Typically, shells are comprised of gelatin, plasticizers, and purified water. For most of softgel’s commercial history, gelatin from animal origins has offered the industry the performance and safety they needed to encapsulate most compounds successfully. 

Despite the legacy of animal-sourced gelatins, development continues. To enhance softgel structure and functionality, for example, manufacturers introduced softgel shells combining bovine and porcine gelatin. To offer consumers even more choices, gelatin from fish has emerged as an attractive alternative to bovine and porcine sources. Formulating shells with gelatin from fish is being leveraged as a market differentiator and the means to appeal to socially conscious consumers who eschew eating meat or object to sourcing raw materials from mammals.⁷ 

Dietary and Other Norms Prompting Softgel Innovation 

Despite the advantage animal-sourced gelatin delivers to commercial softgels, the increasing adoption of vegan and vegetarian diets by more consumers is driving softgel innovation back to its roots. Plant-based softgels offer developers clean label ingredient options and the opportunity to provide consumers with nutraceuticals free from protein, gluten, sugar and GMOs. Early plant-based innovation from the industry saw the introduction of carrageenan, an extract from seaweed, non-gelatin-based capsules using plant-based polymers, starch, hydroxypropyl methylcellulose or Hypromellose HPMC, and gums such as pullulan.5 Although the development and refinement of these materials continue, next-generation plantbased softgel technologies are coming online that are more functional and purpose-built for delivering nutraceuticals in softgels. 

One very recent innovation involves gellan gum technology, a greener, more sustainable alternative to existing carrageenan plant-based softgel technology. Gellan gum is produced via a natural fermentation process, which means it has a lower environmental impact than other products. Gellan gum produces a clear gel that’s less sensitive to heat. In formulation, it helps avoid capsule deformation, the risk of cross-linking with ingredients and discoloration. Further gellan gum provides a robust oxygen barrier that helps ensure stability and extend the shelf lives of active ingredients. 

Sirio Pharma’s studies show gellan gum softgels can encapsulate both single ingredients and complex formulas including suspensions (such as β-Carotene, calcium + vitamin D) with few, if any, compromises. Their versatility extends to pure oil products including EPO, CLA, linseed oil, fish oil, DHA algal oil, vitamin E, phospholipids, phosphatidylserine, vitamin D and more. Formulation Complexity and the Priority of Bioavailability 

Today’s supplement and nutraceutical developers continue to introduce new complex compounds and formulations to markets and consumers. Ranging from probiotics to complex plant proteins and botanicals, research and innovation is helping achieve that through better solubility, bioavailability, and targeted delivery of those compounds. For example, softgels are well known for their ability to deliver poorly water soluble compounds (BCS class II or class IV) orally.⁸ Achieving this is made more complex depending on the active ingredient formulation and the desired softgel dose form. 

Most nutraceuticals derived from natural compounds suffer from poor solubility, low permeability and other factors constraining bioavailability.⁹ Apart from the traditional formulations, many manufacturers and developers are now leveraging novel formulation technologies to differentiate their products and increase market appeal and sales. More importantly, developers are leveraging novel formulation strategies to enhance the efficacy, safety, and patient-centricity of their softgel-based nutraceutical innovations. For example, super-concentrating actives to reduce formulation volume delivers two things: more actives on target delivered in a smaller package. 

Due to early dissolution in pre-enteric secretions, drugs can have trouble reaching good bioavailability in the human body. Because of their inherent material properties, the softgel’s shell formulation can provide excipient-like qualities that ensure actives pass the esophagus successfully, reach deeper into the stomach, or further into the small intestine intact. Specific formulations and coatings can also increase softgel’s enteric delivery capabilities. Advancements in shell formulation technologies continue to make softgels a viable method to deliver actives because they provide a clear path to market for poorly soluble nutraceutical compounds. 

Exceeding Softgel’s Current Limitations and Developer’s Expectations 

Encapsulating probiotic bacteria formulations in softgels has been a notable challenge as these capsules require high temperatures and humidity to manufacture, which can damage probiotics, rendering most probiotic formulations undeliverable in the format. Common softgel shell formulations were also challenged to maintain a market-standard shelf life (typically 2 years) for probiotics, especially at room temperature. Fortunately, refined shell chemistry, formulations and processes, and recent patented innovation enable the commercial manufacture of softgels that combine uncoated probiotic bacteria with at least one oil – e.g., fish oil with either DHA or EPA, in a softgel. 

Lactobacillus and Bifidobacterium are some of the more well documented strains that can be delivered via this methodology in a softgel format. Combining probiotics with fish oil has become a proven approach to successful delivery in the gut. Studies show that Omega 3 has the capability to deliver higher concentrations of probiotics in fewer doses. It’s those kinds of pharma-based unit processes that contract manufacturers are increasingly delivering to support the formulation and delivery of consumer-preferred softgels. 

Softgels: Truly an Easier Pill to Swallow 

Pill fatigue among all consumers/patients is real and it affects dose compliance and other aspects of choice, consumption, and health outcomes.^1,2 No matter how effective the active ingredient may be, it will never deliver its desired effect if it is not taken as prescribed or as recommended. Consumers want their nutraceuticals to be personally and socially ‘responsible’ in every way. To attain those product goals and meet consumer demands, the industry will be increasingly prompted to access advanced softgel technology and more application science from their nutraceutical manufacturing partners. 

References 

1. https://www.keppelhealthreview.com/winter2022/ pillfatigue#:~:text=Pill%20fatigue%20is%20when%20a,they%20 have%20to%20take%20them. 2. https://www.swallowingtablets.com/ 

3. https://www.fortunebusinessinsights.com/nutraceuticalsmarket- 102530 

4. https://www.alliedmarketresearch.com/nutraceuticals-market 

5. https://www.grandviewresearch.com/press-release/global-softgelcapsules- market 

6. https://detroithistorical.org/learn/encyclopedia-of-detroit/schererrobert- pauli 

7. https://www.globenewswire.com/en/news-relea se/2022/02/25/2392158/28124/en/Global-Gelatin-Market-Growth- Trends-to-2026-Fish-Gelatin-as-an-Attractive-Substitute-to- Mammalian-Gelatin-Drive-Massive-Consumer-Interest.html 

8. https://www.sciencedirect.com/science/article/abs/pii/ S0022354915324588 

9. https://www.researchgate.net/publication/318590249_Solubility_ of_Nutraceutical_Compounds_in_Generally_Recognized_as_ Safe_Solvents_at_298_K