Overcoming problematic production issues in nutraceuticals


The development of solid dose products into a formulation that can then be compressed in a modern tablet press at high speed can cause a number of technical challenges. Rob Blanchard, R&D Manager and Trevor Higgins, Technical Expert at I Holland look at the issues

Tablets are one of the most successful forms of administering medicines and also offer an efficient means of reducing powders and granules into a compact product. The tablet is versatile, small, robust and accurate, and can be consistently mass-produced at high speeds. The problem of producing solid dose nutraceuticals is under intense scrutiny as the industry progresses toward stricter regulations and higher standards, which are, in some ways, identical to those used for the pharmaceutical industry.

The most common multivitamin formulas contain up to 50 active ingredients and 2–8 excipients, including coating ingredients. Pharmaceutical formulations tend to contain 1–4 actives and 5–6 excipients. These higher numbers of active ingredients in nutraceutical formulations bring challenges related to particle size, flow, compressibility, moisture sensitivity, ingredient interaction, content uniformity and quality control (QC) testing.

For example, some active ingredients may be available in granular form, whereas some may only be available in fine powder form; some may be hydrophilic and others hydrophobic. Because of this, the ingredient blend may have many different particle sizes and ingredients with a variety of characteristics. Ingredient blends can also have separation and flow issues. Tablet production from these blends can result in capping, sticking and different patterns on the faces of tablets during compression, as well as basic content uniformity problems.

The addition of natural ingredients in nutraceuticals, which have a tendency to be unrefined, abrasive, corrosive and hard, results in the components used to process them being subjected to damage

Tablets are produced using punches and dies in a tablet press wherein the ingredients of the product, usually in powder or granule form, are bonded into a solid shape by compaction at high forces. This technology has been used for many years in the production of pharmaceutical tablets to deliver drugs and medicines. Because of its reliability, this process has also been adopted for the production of some confectionery items, and other compacted products such as detergent tablets, sterilising tablets, cosmetics, catalysts and chemicals, as well as nutraceuticals. However, as mentioned previously, this brings its own challenges.

The addition of natural ingredients in nutraceuticals, which have a tendency to be unrefined, abrasive, corrosive and hard, results in the components used to process them being subjected to damage. Tablet punches and dies are the main components that interface with the powders and granules and, as such, have to be robust both metallurgically and in terms of design to withstand the rigours of compacting nutraceuticals. Vitamin, mineral and food supplement tablets tend to be quite large and bulky when compared with pharmaceutical tablets, especially multivitamins. This is to enable sufficient delivery of the beneficial ingredients. They often require high compaction forces to bond the ingredients into a robust tablet, and the tableting equipment is usually run at high speeds for long periods of time to satisfy the nutraceutical industry’s demands for high output and low cost.

Tooling has to have a long life and be antiabrasive and wear resistant

Tooling has to have a long life and be antiabrasive and wear resistant

Nutraceutical formulations normally have more actives present in higher weights than pharmaceutical formulas. The limits of dose size typically result in restricted room for excipients. A typical nutraceutical formulation has 70–90% actives with the balance as excipients, whereas traditional pharmaceutical formulations have 70–90% excipients and 10–30% actives. The fewer excipients and variety of actives in the same formulation make it difficult to achieve certain desired outcomes, such as disintegration time, hardness and friability. Nutraceutical customers are also demanding smaller dosage size and fewer ‘other ingredients’ (excipients), which narrows the options for formulators. As the choice of excipients get narrower, it becomes more difficult to formulate and achieve desired product outcomes.

When developing a nutraceutical product, the formulator is faced with the challenge of delivering the correct quantity of each ingredient into every tablet or capsule. Non-uniform powder flow can negatively affect the distribution of active ingredients from tablet to tablet or capsule to capsule, and cause failure to meet active ingredient claims. Poor compressibility can introduce productivity problems in the tableting process. Attention to the production process and the use of high quality punches and dies (with or without specific antiwear, antistick and anticorrosion coatings) can prevent the time-consuming and frustrating trial-and-error resolution of problems at finished product stage.

Careful design of the tablet shape and form needs to be considered when choosing suitable tooling

Something else to consider is the identification and marketing of the brand. Apart from the packaging, the tablet shape and inscription is often utilised for brand identity and marketing, including shapes and forms, and inscriptions such as logos, product names or codes. This presents another hurdle for the tooling manufacturers. Adding to the challenge, many nutraceutical tablets tend to be produced using neutral colours such as browns and greys with mottled, textured or granular appearances, which can make any embossing difficult to read.

Careful design of the tablet shape and form, and the force applied during compression, needs to be considered when choosing suitable tooling. It is advisable to avoid small, delicate and complex shapes with vulnerable, high stress areas. As well as good design, equal consideration must be given to the selection of materials for the tooling construction. Because of the aggressive nature of some nutraceutical ingredients, the properties of materials are extremely important and must be balanced to give optimum tooling performance and durability. These properties include abrasion and corrosion resistance, compressive strength, hardness and toughness and, also, resistance to chipping and cracking. Tooling has to have a long life and be antiabrasive and wear resistant. To achieve this there are several options.

Raw Materials

Owing to the nature of nutraceutical ingredients, wear and degradation of the tooling will lead to other tablet-making problems, such as adherence of the granules because of the pitted and worn surfaces of the punches, and also ‘capping’ or ‘lamination’ of the tablets, which could prove costly for the nutraceutical manufacturer. The correct choice of material will help to reduce the risk of damage to the punches and dies from the effects of abrasion, corrosion and impregnation of hard granules. There are thousands of steel types available; yet, only a few meet the complex design and functional requirements necessary for tablet tooling.

Wear and degradation of the tooling will lead to other tablet-making problems

Wear and degradation of the tooling will lead to other tablet-making problems

Alternative materials such as tungsten carbide (I Holland’s HPG-TC) and enhancement coatings and treatments (I Holland’s PharmaCote range) should be considered. Commonly used materials for nutraceutical tooling include high carbon, high chrome, cold work tool steels.

Tungsten carbide is often used for the dies to prevent wear and deformation of the die bores. It features a high compressive strength with an extremely high wear resistance. This helps to reduce die bore wear and ringing and lasts longer than conventional die steels.


I Holland’s understanding of tableting science has proven that when coatings are developed correctly, and their beneficial characteristics are matched to those of the formulation, they can help to increase corrosion resistance, wear resistance and prevent sticky formulations adhering to the punch tip faces. I Holland has deployed many advanced techniques such as optical surface profilometry, scanning electron microscopy, X-ray photoelectron spectroscopy (XPS) and nanowear testing equipment to help improve the performance of our coatings.

Traditionally, the most popular coating used within the global tablet tooling industry is hard chromium because of its low cost and general-purpose characteristics in terms of average antistick, anticorrosion and antiwear properties. However, electroplated hard chromium has several disadvantages.

Hydrogen embrittlement: When hard chromium is applied to tooling, a certain amount of hydrogen penetrates the substrate, which decreases the steel’s strength. That is highly undesirable in a component subject to high cyclic loading. To counter this effect, the tools undergo a baking process known as de-embrittlement that reduces, but does not totally eliminate, the unwanted characteristic. Indeed, tooling with hard chromium applied to it can only withstand a maximum of 80% of the designed safe working load that could be applied to an uncoated tool.

Microcracking: Microcracks develop during the plating process when the internal stress exceeds the tensile strength of the chromium, which is hard and brittle. These microcracks are problematic because they provide a porous route to the substrate that will, with time, allow aggressive tablet formulas or cleaning solutions to attack the steel beneath the coating.

Environmental issues: Hard chrome itself is not an environmental hazard, but there are environmental problems associated with the plating process. The main issue is the chromic acid solution used in the process. It generates a waste product that contains hexavalent chromium, a tightly controlled substance that must be disposed of correctly.

To combat these issues, I Holland developed PharmaCote EC, which is a chromium-rich coating that is applied via magnetron-sputtered PVD. With magnetron sputtering, however, the target material is vaporised by exciting the target chromium atoms with a bombardment of gaseous particles. Magnets behind the target material assist in the process. The magnetron sputtering process causes a very smooth (antistick) and dense coating to form, and the process incurs none of the drawbacks associated with applying hard chrome.

Tungsten carbide is often used for the dies to prevent wear and deformation of the die bores

Tungsten carbide is often used for the dies to prevent wear and deformation of the die bores

A specific coating that has been developed to combat problems in the production of nutraceuticals is PharmaCote RS. Because abrasion is such a major problem in nutraceutical tablet manufacture, and the products can contain high quantities of hard, abrasive, sharp edged minerals that when repeatedly compressed can scrape away or penetrate the surface of the tool, the abrasion can lead to the erosion of punch tip detail such as logo embossing and other identification. Eventually, this wear can lead to weight variation, sticking and other issues resulting in the scrapping of the punch.

PharmaCote RS is a resilient surface coating that is applied with electron beam technology. This technology allows a very hard coating to be applied, whilst still giving a very smooth finish. One of the reasons this coating has such fantastic wear resistance is its very high hardness value (3000 HV). This coating is only applied to the punch tip as it could cause damage or wear to the tablet press if the whole punch was coated. The compression rollers have a much lower hardness than PharmaCote RS. Following extensive development work, this coating was tested in the field on a nutraceutical product that was destroying some of the company’s competitor’s punches.

Case Study

In January 2008, a leading nutraceutical manufacturer was experiencing serious issues with a particularly abrasive vitamin formulation. Many nutraceutical products can be abrasive in nature, but this particular compound was causing extreme difficulty. Only 22 million tablets could be compressed before the tooling was worn to such an extent that it was deemed to be unserviceable. This not only necessitated the purchase of new punches but also incurred the associated downtime inherent with replacing and setting up 37 tooling stations. I Holland was challenged to find a solution to extend the life of this tooling. Through its continual research and development programme, I Holland was in the final stages of developing a highly promising new antiabrasive coating. This formulation presented an ideal opportunity to trial the highly wear resistant PharmaCote RS.

The Trial

A compression trial was set up at the customer’s premises and I Holland dispatched stations of the new RS coated punches for trial along with one of their iNSPECT camera systems. Photographs were taken for record and stored to enable comparisons to be made during the trial. The goal of this trial was to see just how far the useful life of the tooling could be extended by the use of a coating. The RS coating was tested with the same abrasive formula against HPG-P and a more common chromium nitride (CrN) coating.

Representatives kept in close contact during the trial, visiting on a regular basis to check progress. When the results started to take shape, RS emerged as a clear winner. The more commonplace CrN coating was shown to fail between 19.5 and 21.1 million tablets, the premium steel was withdrawn between 21.1 and 22.8 million tablets but the PharmaCote RS was still serviceable at an astonishing 44,010,000 tablets. This represents an approximate 93% increase in the lifespan of the tooling when compressing this formulation.

The Benefits

These spectacular results translate into valuable cost savings and productivity increases for the customer. This coated tooling now lasts nearly twice as long before it requires replacement, with longer run-times and less need for costly downtime owing to tooling replacement. In addition, product yield has also increased as the presses need to be set up fewer times. Since these trials, PharmaCote RS coated tooling is now being used successfully at three other locations, manufacturing the same range of nutraceuticals and I Holland has released PharmaCote RS to assist customers combating abrasion worldwide.


The development of solid-dose nutraceutical products into a formulation that can be compressed in a modern tablet press, with both speed and quantity, can be a complex and problematic procedure. With certain considerations and measures in place, it can be achieved successfully. As nutraceutical formulations nearly always have more actives present at higher concentrations than pharmaceutical formulas, the room for excipients is restricted, making it harder to formulate. Consideration must also be made to deliver the correct quantity of each ingredient, in each tablet. This can cause failure to meet active ingredient claims. This is where choosing the correct tooling comes into its own. By choosing the right quality punches and dies, problems during manufacture can be prevented.

Detailed design is essential nowadays to produce robust nutraceutical tablets with tailor-made properties. Tablet manufacturers should not overlook tablet design because it is key to the quality of the end product. Good tablet design is extremely important, as it has an impact upon anticounterfeiting, tooling strength, coating, durability and functionality. It also helps to avoid tablet sticking, picking, lamination, capping or premature tooling failures right at the beginning of the process by ensuring a problem free end product.

Getting all these factors right is imperative to producing a ‘good’ tablet. The process is something that should not be rushed, it needs to be well thought out and considered; good tablet design is essential to prevent downstream problems, produce high quality tablets and maximise the efficiency of the tableting process. All these factors are important to consider if you want to overcome problematic production issues in the manufacture of nutraceuticals and should be explored from the initial conception of a tablet.