What is pelletization, and how is it advancing nutraceuticals and dietary supplements?

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Nutraceuticals are gaining popularity as an effective tool for maintaining health as public awareness of the advantages of health supplements grows. According to market analysis, the global nutraceutical segment is anticipated to increase in value from $450 billion in 2021 to $746 billion by 2028, with a projected compound annual growth rate (CAGR) of around 8.8%.¹

A variety of products are now included within the nutraceutical category. Companies are implementing new delivery systems to further expand their nutraceutical ranges. Many are taking inspiration from pharmaceutical manufacturing and adapting these innovative techniques for the delivery of nutraceutical products.

Tablets and capsules are the most common formats for pharmaceutical and nutraceutical oral delivery systems. Currently, these formats are undergoing different modulations. In particular, many are adapting one of the most appealing technologies used in controlled drug delivery: pelletization.

Pelletization and Nutraceuticals

Pelletization has attracted a great deal of attention across the sector. It is now being applied to nutraceuticals in the same way as pharmaceuticals, to alter the release pattern of formulations.

The pelletization process formulates active ingredients in free-flowing spherical beads, granules, or pellets, which can be coated to provide the required modified-release properties. Additionally, this process offers numerous other benefits to manufacturers, including the ability to combine incompatible components in a single dosage form.

There are different methods for pelletizing active ingredients, including: extrusion spheronization, fluidized bed coating, dry powder layering, and spray congealing.

The pellets prepared in the process are either made directly from the active nutraceutical ingredients (ANI), or they can be base pellets that act as a vehicle for later stacking of active material. A product may comprise 90% of the ANI along with the additives, or base pellets.

Two types of base pellets are used for stacking. The first are neutral starter pellets, which are inert and usually used to avoid interaction with the ANI. Examples include sugar spheres, MCC (microcrystalline cellulose) spheres, wax-based spheres, silicon dioxide spheres, lactose-starch/lactose-cellulose spheres, and rice-based spheres. The other type of base pellets are functional starter pellets that actively promote formulations by enhancing the ANI’s solubility, dissolution, and stability.

Pellet preparation enables the formulator to alter the product’s properties and release pattern. It is possible to incorporate immediate- and controlled-release delivery mechanisms in pellets by using fast-disintegrating pellets and pellets coated with different polymers, respectively. For ingredients with poor solubility, pellet techniques help to deliver the desired effect by combining excipients that enhance solubility—for example, curcumin pellets. Additionally, it is possible to achieve sustained release by coating the pellets, as in the example of caffeine pellets.

Encapsulation of Nutraceutical Pellets

The most effective way to deliver pellets in the smallest container is in capsules. Many nutraceutical manufacturers adapt the capsule dosage form to deliver their product, as it provides better tolerance over other dosage forms. Capsules also serve as site-specific and prolonged-delivery systems. For example, sustained-release caffeine pellets in a hard capsule can slowly release caffeine into the body over a prolonged period, offering a sustained release of the caffeine’s effect.

There are further examples of active nutraceutical ingredients formulated in pellets and encapsulated in hard capsules which are currently on the market. These include:

• Soy protein pellets in capsules
• Emblica officinalis (amla) pellets in capsules
• Asparagus racemosus (shatavari) pellets in capsules

Examples of HPMC (vegetarian) capsules:

• Zinc pellets in capsules
• Crocus sativus (saffron) pellets in capsules
• Vitamin B6 pellets in capsules

Pellets generally offer an advantage over other oral dosage forms, in the effective administration of multiple incompatible materials at the same time. It is possible to combine two or more release patterns in one capsule as pelletization is adopted. Additionally, it is feasible to incorporate two types of pellets with the different ANIs—in their active form alongside liquid in a single capsule.

The demand for manufacturing technologies that overcome formulation issues such as stability, absorption, and permeability has increased because the market requires advanced formulations. For nutraceutical products, it is difficult to add two incompatible active ingredients in a dosage form such as a tablet; however, two different pellets in a hard capsule can resolve this challenge. By doing this, a synergistic therapeutic effect can be achieved using two different types of pellets. Nutraceutical formulations with combination fills may come in the form of liquid + pallets or liquid + capsules, allowing two incompatible active ingredients to be combined and have a synergistic effect.

In particular, the liquid + pellet combination dosage form can produce various profiles, such as immediate release dissolved in liquid and delayed release in pellet form. For example, take a complex pellet containing vitamins A, D, E, and B. It is also possible to add two different nutraceutical pellets combined with liquid nutraceuticals for combination therapy.

Another combination-fill technique involving liquid + capsule helps to minimize stability issues. It is the most common method for combination fill and consists of one active ingredient dissolved in the carrier solvent and the other, in pellet form, enclosed in a smaller capsule that is dispersed in the liquid. For example, with vitamin A, E, and C capsules, the capsule can contain the nutraceutical active ingredient in pellet form to further aid the sustained release of the ANI.

Advantages of Pelletization

There are definite advantages to pelletization techniques and formulation. Pelletizing active nutraceutical ingredients can help improve the efficacy of a formulation by modulating the solubility and bioavailability of lipophilic and moderately-water-soluble active ingredients. It is also possible to achieve sustained release for the active ingredient by formulating it in pellets. The therapeutic effects of the ANI can be enhanced by the pellet formulation as the pellet disintegrates in the GI system.

There are additional advantages. Nutraceuticals with an unpleasant taste can be masked in pellets to make a product more palatable and increase consumer compliance. And using colored coating material to manufacture the pellets will not only improve the appearance of the formulation but will also provide the product with uniqueness to appeal to consumers and provide brand recognition. This color mix and the aesthetic appeal of the pellet-embedded capsules can attract consumers and, in turn, support product marketing.

HPMC Capsules: A Vegetarian Alternative

It is feasible to encapsulate nutraceutical pellets in gelatin (HPMC, hydroxypropyl methylcellulose) or hypromellose capsules; however, HPMC is considered the better option as many of the challenges faced by nutraceutical manufacturers, mentioned below, can be overcome with these capsules.

The major challenge for nutraceutical providers is maintaining the stability of the compound and the overall aesthetic of the product. Many of the vitamins (vitamin C, thiamine, vitamin B12, pantothenic acid), amino acids (acetyl-L-carnitine HCl, L-arginine base), enzymes and co-enzymes, and certain minerals and their active salt forms are moisture sensitive, and HPMC capsules offer the better final product owing to its low inherent moisture content. The growing trend in vegetarian and clean-label capsules makes the HPMC capsule a safe choice.

Summary

Pelletization is a game-changing technology for the nutraceuticals market. Enabling a wide range of delivery formats, along with customer compliance, are inherent benefits making it the delivery system of choice for many nutraceutical manufacturers. This technique is leading the way to the development of novel delivery systems, which create new and emerging opportunities for the sector.

About the authors

Jnanadeva Bhat, PhD, is head of formulation R&D (Pharma & Nutra) at ACG Group. Bhat has been associated with the pharmaceutical industry for more than two-and-a-half decades. As a product formulator, he has worked on various dosage forms that include tablets, soft gelatin and hard capsules, injectables, and lyophilized formulations. At ACG, he heads the formulation R&D lab where he primarily leads new product development projects and customer interface.

Manali Dalvi, lead, white papers, formulation R&D (Pharma and Nutra), is part of the Capsules R&D team at ACG. Her primary responsibilities include writing and publishing scientific research articles and developing segmented solutions and technical content as part of thought-leadership programs. She is also involved in all of the company’s industry- and institute-related collaborations and research activities.

Reference

1. Growth Scope of Nutraceuticals Market Size Worth USD 745.5 Billion by 2028 at 8.8% CAGR- Industry Trends and Forecast Report by Zion Market Research. News release. PR Newswire; April 20, 2022. https://www.prnewswire.com/news-releases/growth-scope-of-nutraceuticals-market-size-worth-usd-745-5-billion-by-2028-at-8-8-cagr---industry-trends--forecast-report-by-zion-market-research-301529003.html