Vegan alternatives in encapsulation: HPMC vs. pullulan and classic gelatin

Encapsulation, i.e. enclosing an active substance in a capsule shell, is a key stage that determines the stability and ultimate efficacy of a medicine or dietary supplement. Although gelatin has dominated the market for decades, modern pharmacy is now facing new physicochemical challenges—such as the hygroscopicity of difficult active ingredients—as well as growing consumer expectations for 100% plant-based products. The answer to these needs is modern vegan shells: hydroxypropyl methylcellulose (HPMC) and pullulan. Which one should you choose for your product? We present a detailed technological comparison.

Gelatin capsules – a proven standard and its technological limitations

Gelatin, obtained from animal-derived proteins, served for years as the starting base for the pharmaceutical industry. Its greatest advantages are very good oxygen barrier properties and a low production cost. Gelatin capsules dissolve quickly in the acidic environment of the stomach, ensuring immediate release of the contents. Despite these advantages, research and development (R&D) departments are increasingly looking for alternatives, and the reason lies in specific technological limitations:

• relatively high natural water content – a gelatin shell usually contains 13–16% moisture, which may cause reactions with ingredients that are particularly sensitive to water;
• risk of cross-linking – in the presence of certain substances (e.g. aldehydes or reducing sugars), a water-insoluble film forms on the surface of the capsule, delaying disintegration and release of the active substance in the stomach;
• lack of acceptance by vegans and vegetarians – an animal-derived raw material (bovine or porcine) excludes the product from plant-based ranges, and standard gelatin does not always meet Halal and Kosher certification requirements.

Worth knowing: The phenomenon of cross-linking is one of the most common problems observed during dissolution testing of gelatin capsules. The resulting film (the so-called pellicle) can significantly extend the capsule disintegration time, which may lead to failure to meet the pharmacopoeial specification for active substance release. This is a key argument when selecting a shell for sensitive formulations.

HPMC (cellulose) capsules – masterful protection against moisture

Hydroxypropyl methylcellulose (HPMC), also known as hypromellose, is a semi-synthetic polymer obtained from plant cellulose. It has become the most popular vegan alternative to gelatin, and its advantage stems primarily from a different physicochemical profile. Unlike gelatin, HPMC is characterized by a much lower water content—usually at the level of 4.5–6.5%.

This feature translates into specific production benefits:

• resistance to cracking in a dry environment – HPMC does not become brittle at low humidity, unlike gelatin;
• absence of cross-linking – cellulose shells do not exhibit cross-linking reactions, eliminating one of the main problems associated with gelatin;
• compatibility with hygroscopic ingredients – the low moisture content makes HPMC ideal for encapsulating water-sensitive substances, such as probiotics, minerals, or enzymes.

Eubioco uses both standard HPMC capsules and their advanced variants, such as DRcaps. This type of shell limits the exposure of sensitive active substances to the acidic environment of the stomach, delaying their release compared with a standard HPMC capsule. It is worth emphasizing, however, that DRcaps are not enteric capsules in the pharmacopoeial sense—where the product specification requires validated enteric protection, a dedicated enteric coating must be used.

Pullulan (Plantcaps) – a vegan oxygen shield from natural fermentation

Pullulan is a 100% natural, water-soluble polysaccharide produced by fermentation carried out by the fungus Aureobasidium pullulans. It is a gluten-free, non-genetically modified (non-GMO) raw material and free from typical allergens, which makes it an attractive option for premium brands and clean-label products.

The most important technological advantage of pullulan is its very low oxygen permeability. Independent scientific studies confirm that pullulan-based shells are characterized by one of the lowest oxygen permeabilities among biopolymers used in food and pharmaceutical packaging and coatings (Chen et al., 2017; Reji and Roy, 2026). Commercial suppliers (e.g. Lonza Capsugel) also communicate a significantly higher oxygen barrier for pullulan shells compared with HPMC and gelatin; however, these are internal manufacturer data, published without disclosing detailed measurement conditions (temperature, relative humidity, wall thickness)—in the case of formulations where stability is critical, we recommend confirming the actual barrier parameters in your own R&D tests. Regardless of the exact scale of the differences, pullulan remains the material with the best barrier properties among the vegan shells discussed, making it an interesting option for supplements containing ingredients prone to strong oxidation, such as:

• oxygen-sensitive vitamins (including A, C, and E);
• unsaturated fatty acids (e.g. omega-3);
• probiotics and other sensitive active substances that are easily oxidized.

However, choosing pullulan involves specific technological and economic trade-offs that are worth taking into account already at the formulation design stage:

• higher raw material cost – pullulan is usually 3–5 times more expensive than HPMC, which directly affects the unit cost of the finished capsule;
• slower disintegration in water – compared with gelatin and HPMC, the pullulan shell dissolves more slowly, which may be a significant limitation for formulations requiring immediate release of the active substance;
• limited availability of large sizes – pullulan capsules are less readily available in the largest formats, which is worth verifying already at the production scale planning stage.

Worth knowing: Both HPMC and pullulan are raw materials of plant or microbiological origin, which means they naturally fit the requirements of vegan and vegetarian diets and commonly obtain Halal and Kosher certifications. In the case of animal gelatin, compliance with these requirements is not self-evident and requires the use of specially certified raw materials.

The table below organizes the most important parameters of the three shells discussed, making it easier to make a technological decision:

Parameter	Gelatin	HPMC	Pullulan
Oxygen barrier	Very good	Moderate	The best among the shells discussed (confirmed in independent scientific literature; the supplier reports even higher values in its own tests)
Moisture level in the shell	High (13–16%)	Low (4.5–6.5%)	Low
Resistance to cross-linking	Low (risk of cross-linking)	High	High
Raw material cost (approx.)	Lowest (reference point)	Medium	Highest (approx. 3–5× HPMC)
Disintegration time in water	Very fast	Fast	Slower than gelatin and HPMC
Vegan / Halal / Kosher status	No (animal origin)	Yes	Yes
Main application	Standard immediate-release forms	Hygroscopic ingredients (probiotics, minerals)	Ingredients sensitive to oxidation

Eubiocap innovation – a breakthrough in the formulation of difficult ingredients

Selecting the right shell material is one thing, but the real technological challenge is combining ingredients in one product that do not tolerate each other. Eubioco’s answer to this problem is its proprietary Eubiocap technology—a “capsule-in-capsule” system.

In practice, this technology involves placing a smaller capsule—most often filled with a liquid or oil-based lipophilic form (e.g. omega-3 acids or other oxidation-sensitive ingredients)—inside a larger capsule containing a stable dry form in the form of powder, granules, or pellets. This structure physically separates ingredients that are chemically incompatible or mutually sensitizing, limiting reactions such as oxidation, hydrolysis, or moisture migration between phases.

Placing one capsule inside another involves natural volume limitations—the smaller capsule occupies part of the space in the larger shell, reducing the available volume for the dry form and requiring precise selection of the sizes of both components already at the formulation design stage. The integrity of the finished product is additionally ensured by banding, i.e. applying a sealing band along the joint between the cap and the body of the larger capsule—this protects the product against accidental opening and confirms batch consistency during transport and distribution.

As a result, Eubiocap provides:

• staged release – individual ingredients are released in a defined sequence and at a defined time, in line with the formulation assumptions;
• stability and separation of ingredients – substances sensitive to mutual contact remain physically isolated throughout the entire storage period, reducing the risk of degradation reactions;
• market advantage (USP) – the ability to create a unique, multi-ingredient product that is difficult for competitors to copy.

Choose the optimal form for your product with Eubioco

There is no single, universally best capsule shell—the right choice depends on the characteristics of the specific active substance, the expected release profile, and brand positioning. The technologists at Laboratorium Galenowe Olsztyn, part of the Eubioco group, will advise whether your product needs a standard gelatin capsule, protective HPMC or DRcaps, or the Plantcaps pullulan oxygen shield.

We carry out the entire process in rigorous quality standards, confirmed by GMP and ISO 22000:2018 certifications, which guarantees the safety and repeatability of every batch. Are you looking for a partner who will help select the optimal form for a demanding formulation? Contact us at sprzedaz@eubioco.eu to discuss your project, receive a quotation, and plan R&D tests.

REFERENCES

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