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HPMC: The Impossible Capsule


Developing plant-derived alternatives to animal-based products is never easy. But for capsules, the solution not only meets expectations but exceeds them.

Non-GMO Project

By now, the vegetarian and vegan revolution is in full swing. Everything from oat milk to vegan ice cream showcases growing consumer demand for products that substitute conventional animal-based ingredients with those derived from plants. Getting it right—finding a formula with a pleasing taste, texture and aesthetics—is seldom simple. They don’t call it the ‘Impossible Burger’ for nothing.

The plant-based push has also impacted one of mankind’s oldest delivery devices: the capsule.

The capsule industry began researching and developing plant-based capsule substitutes years before food processors responded with vegan products. The search for an adequate animal-free substitute took time, effort and innovation.

The Plant-based Capsule Journey

Why did it take so long? Well, for one thing, the vast majority of capsules used for pharmaceuticals, nutraceuticals and other nutrition products are composed of gelatin. There is good reason for this, as gelatin is easy to produce, homogenous and, from a manufacturing versatility standpoint, incredibly robust. Gelatin withstands the mechanical stresses of filling and packaging operations, provides exemplary product protection, and avoids co-mingling with its contents. In short, gelatin “plays well.”

What gelatin most certainly is not, however, is vegetarian. This presents an issue for consumers seeking to remain vegetarian or vegan either for religious beliefs or simply as a healthy lifestyle choice. As with the food sector, it took years, even decades, for the capsule manufacturing industry to begin perfecting formulas that adequately substitute plant-based products for animal-based ones like gelatin. Today, the closest thing that exists are capsules composed of hydroxypropyl methylcellulose, better known by the acronym HPMC.

Savvy nutritional products manufacturers knew that, to fully embody the clean, natural image so important to modern consumers, they had to look past delivering their powdered herbs, probiotics, dietary supplements and nutraceuticals in capsules comprising animal skin and cartilage. There had been, quite literally, a connective tissue disconnect between traditional health products and the capsules in which they’ve been traditionally contained.

Was finding a viable plant-based substitute capsule alternative difficult? You bet it was. But as we’ll explore, though not perfect, HPMC turned out to be one heck of a substitute success story. Today, it is the second most prevalent capsule type in the world, and its popularity in the nutrition sector is particularly prolific. This is because HPMC does more than match its animal-based counterparts’ well-earned reputation for reliability, but in some cases actually exceeds it.

The HPMC Capsule Solution

HPMC capsules are produced via a renewable plant-based resource, cellulose, typically obtained from wood or cotton. Chemically, it is a methyl and hydroxypropyl group substituted with anhydroglucose units, which are sourced from cellulose.

HPMC is compliant with the norms of major pharmaceutical regulatory bodies, and is permitted as a food additive for human consumption. For nutraceutical brands stressing products with plant-based origins, they can be certified by designation authorities such as Vegan USA and Vegetarian Society UK, as well as organizations that bestow kosher and halal certifications. Non-GMO (genetically modified organism) verification also is available.

There are two manufacturing methods that can be employed to produce HPMC capsules, differentiated by the temperature of the pin used to mold them. With a cold process, gelation occurs between 20 and 25 degrees Celsius. However, to achieve this gelling, co-gelling agents must be added to the composition. Often, machines used to produce gelatin-based capsules cannot be utilized to create HPMC versions, as they lack the ability to accomplish this mission-critical step.

During a hot process, gelation occurs between 70 and 80 degrees Celsius. The added heat eliminates the need to add gelling agents, making it a more functionally viable process for existing capsule production machines, whose features are geared toward creating legacy gelatin-based versions. Once this baseline machinability metric is met, HPMC’s value shines through in a variety of product and environment-driven circumstances.

Additional Plant-based Capsule Manufacturing Considerations

An understanding of the most typical obstacles to successful encapsulation is key to determining how animal-based capsules might be replaced with vegan-friendly ones. Underpinning each of these is the fact that, from initial capsule filling to packaging to the often complex supply chain journey that ends on the tips of consumers’ tongues, an encapsulated product must remain safe, effective and true to its brand promises.

Hygroscopic and Moisture-sensitive Products

Moisture is arguably the most significant enemy of encapsulated products, whether they be pharmaceutical or nutritional, because water and other forms of moisture are the likeliest path to degradation. A term meaning “water-absorbing,” hygroscopic formulations seek to absorb water wherever they can to their own dismay—a sort of suicide by self-sought saturation. From an encapsulation standpoint, this means that such products will attempt to pull moisture from the capsule itself, which can make the capsule brittle and therefore prone to leakage or breakage. Even worse, the formulation itself may be moisture-sensitive, introducing the possibility of damaging not just the capsule but the product itself.

As detailed in the subsequent section, HPMC capsules have a lower overall moisture content than do gelatin capsules, which can present a major benefit for protecting the integrity of nutraceutical products.

Relative Humidity

Changes in relative humidity, which can occur either inside the capsule itself or in the outside environment, especially along the supply chain, also can adversely affect stability. Depending on which way the humidity fluctuates, the result can be either brittle or soggy capsule shells.

Because gelatin capsules have a comparatively higher moisture content—typically 13 to 16 percent—with water acting as a plasticizer (essentially, a molding agent), when they are stored at relative humidity under 40 percent they lose water and become less flexible, yielding brittleness. A similarly resulting vulnerability can occur with moisture-sensitive products. The most common method of protecting such formulas is using desiccants. Of course, this can artificially create the same scenario in which a drier external environment pulls water from capsules, leaving them brittle.

By contrast, HPMC capsules have a moisture content ranging from 3 to 8 percent, making them an attractive option for hygroscopic and moisture-sensitive formulations. This also makes them less susceptible to low-humidity-related adverse reactions, since the relative humidity in the surrounding environment would need to be far lower to exact any significant toll.

Advanced Machinability

Previously, we touched upon the basics of machinability as it relates to capsule creation. Now that we’ve discussed HPMC capsules’ comparably low moisture content, a more in-depth analysis is possible. Simply put, with HPMC capsules the mechanical properties do not depend upon moisture content. Even under dry conditions, HPMC capsules robustly maintain adequate elasticity.

Elastic modulus is a term used to describe the overall elasticity of capsules. It’s complicated but, briefly, it is calculated by dividing compression stress by the corresponding compression strain value. Tests indicate that HPMC displays low elastic modulus, indicating a greater elasticity and comparably higher degree of recovery time to applied stress. In layman’s terms, HPMC capsules “bounce back” effectively, maintaining its protection effectiveness without allowing adverse conditions to compound upon one another.


Also known as polymerization, cross-linking is another deleterious effect that HPMC, simply by its composition, all but eliminates.

Certain products, excipients (like bulking agents) and storage conditions can lead to cross-linking in gelatin capsules, which occurs due to chemical reactions between the amine group lysine—a building block of protein typically found in gelatin—and a similar amine group in neighboring molecules, including those in the encapsulated product. Polymerization also can occur under certain high-stress conditions, including exceedingly high temperatures and humidity.

Cross-linking is particularly problematic for any nutrition product—probiotics come to mind—in which controlled release capabilities are paramount. This is because cross-linking renders gelatin capsules resistant to dissolution, diminishing the product’s deliverability and therefore its efficacy.

HPMC capsules significantly reduce the risk of cross-linking. This is because HPMC has a chemical structure that does not react with aldehydes, which in turn make them compatible with a wider range of encapsulated products.

The future is bright (and colorful) for HPMC; a growing and booming consumer need for natural products combined with continual refinements are making formulation simpler and more attainable for manufacturers. We’ve proven the Impossible Capsule is in fact possible and the growth potential is endless. NIE

Evelyn Reinson is an international marketing manager at ACG, responsible for global marketing strategies of the company’s product range of capsules, films & foils, engineering, and inspection worldwide. www.ACG-world.com.