Dietary Supplement Tablet Manufacturing

The trend in consumer preference for supplement delivery form might have long ago begun its migration to capsules from tablets, but the compressed pill form still has its admirers. In fact, the question of preferred dose form seems to have morphed into one of innovation, as time-release, taste-improving and quality-heightening technologies have become more highly desired. Tablets also offer supplement consumers a dependable and economical option, compared to generally more expensive capsules.

With this in mind, INSIDER turns its attention to tableting, to find out what is new and improved, and what goes into making high quality tablets. We dialed up two tableting experts from Nutritional Laboratories International: Brad Nylander, vice president and chief operations officer (COO), and Hunter Hickes, technical services supervisor. Nutritional Labs is a full-service contract manufacturer for the dietary supplement and pharmaceutical industries, manufacturing vitamin, mineral, botanical and specialty formulas in various shapes and sizes of hard and chewable tablets in both short- and high-volume runs since 1997.

INSIDER: There is so much about encapsulation technologies these days, but what is going on in tableting? Are there innovations in materials and equipment that are changing how supplements are made into tablets?

Nylander and Hickes:

Surprisingly, many of the machines, raw materials, excipients and techniques used to produce nutritional supplement tablets have remained unchanged for the last 20 years or so. That said, there have been a number of innovative specialty excipients that have been introduced into the marketplace over the past decade. Along with this, the general quality of excipients has continued to become better. Mechanically, there are now highspeed, fully automated tableting machines capable of ejecting individual tablets that are out of weight and/or hardness specification. Newer machines now have interchangeable turrets that allow tooling changeovers to happen very rapidly. An operator can be running one size tablet (run #1), while maintenance personnel are preparing a second turret with different tools to quickly replace the current turret when run #1 is completed. Fluidbed granulation is also a fairly recent technology that is very useful for creating directly compressible agglomerations without having to undergo a true “wet” granulation.

INSIDER: How important is granulation in tableting, and when would wet granulation be used in lieu of dry granulation?

Nylander and Hickes: The term “granulation” simply means to create and control the size of the particles in a powder or blend, usually going from a smaller grain size to a larger grain size. Typically, the rule of thumb in tableting is to limit the amount of “fines” (fine particles that are less than a 140- or 200-mesh, depending on who you talk to) in the blend. Raw materials typically used in nutritional supplements include powders and extracts that are commonly very fine-grained. Granulating these ingredients can help produce more robust tablets (allow increased hardness, lower friability, and faster disintegration times).

There are many methods that can be utilized to granulate a raw material or a blend of ingredients. In general, the pharmaceutical industry tends to favor true “wet” granulation over dry granulation, or direct compression. There are many reasons for this; chiefly, the moisture content of the final blend and the particle size can be precisely controlled, and binders can be distributed throughout the blend more efficiently than either of the other two methods. Direct compression blends—blends that are more or less a collection of raw ingredients, some binder (MCC), some lubes (stearic acid or magnesium stearate), and a flow aid (silica)—tend to have a large variation in the size of the particles in the blend. This can cause segregation issues on the tab press or in the hopper. This in turn, can cause a large variation in the active profile from tablet to tablet. Wet granulation would be preferable to dry granulation (i.e. roller compaction) when the raw materials that require granulation are fibrous and resist physical densification, as well as in instances where the formulator would want to add a binder and control the moisture content of the final granulation.

INSIDER: Are there other technologies from the pharmaceutical world that could help dietary supplement tableting?

Nylander and Hickes: True wet granulation is probably the most important technology that can (and does) cross over from the pharmaceutical world into the realm of dietary supplements. Successfully implementing this process requires technologically advanced equipment and personnel with a high degree of technical skills and knowledge. An understanding of the chemical effects of wet granulation on every blend is as critical a parameter as the physical results that a formulator may want to achieve. As such, true wet granulation is not as common a process as direct compression in the nutraceutical industry.

INSIDER: Is controlled- or time-release as much a factor in tableting as it is becoming in encapsulation? Also, what role do effervescent tablets play in the current supplement market?

Nylander and Hickes: There are ways to create tablets that will exhibit a true “time-release” active profile by using specialty coating materials and/or incorporating gelling agents like Sodium Carboxymethylcellolose at appropriate input levels. Also, I believe there will always be a place for effervescent tablets. The active ingredients (type and amount) that can be delivered via dissolution in a glass of water are, however, limited. Mild effervescence can also be useful for improving the mouthfeel of chewable tablets.

INSIDER: How much does a tablet’s coating affect the function of a tablet? Do certain coatings enhance consumer compliance?

Nylander and Hickes: A tablet’s coating can affect the function of a tablet dramatically. These effects go beyond swallow-ability and product recognition. There are enteric and time-release coatings available on the market.In my opinion, these functions have not been marketed to the extent that they could be. Customer compliance can be enhanced by certain coating designed to cover bad taste and also improve swallow-ability of larger tablets. Coatings can also cover or mask foul odors exhibited by some herbal ingredients.

INSIDER: Do certain ingredient categories or individual ingredients pose special challenges to tableting? Which ones, and why?

Nylander and Hickes: Yes, there are various materials that do cause headaches when trying to tablet them. Fibrous botanicals are sometimes very difficult to deal with and require special granulation methods to achieve compressibility. Think of fibrous ingredients as though they were hay. Imagine trying to compress a bale of straw into a tablet. Fibrous ingredients do not have good compressibility and do not allow bonding at the molecular level, which is required to hold a tablet together.

Minerals and crystalline ingredients, like glucosamine, can also be notoriously hard to work with. Many folks who do not fully understand how raw ingredients are compressed into a tablet think that any “granular” material is good for tableting. This is not always the case, especially when dealing with materials that have a crystalline structure such as acetic acid, glucosamine and sugars like xylitol. These ingredients require special processing to create a granulation that is a directly compressible form of those ingredients.

INSIDER: As formulations have become more extensive, are tablets averaging a larger size, and are there particular challenges to making large tablets?

Nylander and Hickes: Yes, as tablets become larger, they become more susceptible to attrition in the coating pan. This has to do with how forces are applied during the making of a tablet and the simple fact that larger tablets have more weight, and thusly impacts that occur during handling and coating have more force than they would have with smaller tablets. Larger tablets, in general, require higher hardness in order to have the robustness needed to withstand handling, coating, and bottling.

INSIDER: What GMP (good manufacturing practice) options are there for tableting supplements, and do you adhere to GMPs from any outside organization?

Nylander and Hickes: There are current GMPs for manufacturing tablet supplements. These cGMPs are currently at the level of food manufacturing, a level of regulation considerably lower than drug manufacturing. Nutritional Laboratories follows cGMPs that will comply with the nutritional supplement cGMPs soon to be released by the Food and Drug Administration (FDA). We have been audited and certified by NSF, an independent organization that has designed its audit procedure and certification criteria around their interpretation of the new cGMPs.

INSIDER: What can product formulators do before the tableting stage to make the process go smoother?

Nylander and Hickes: There are many procedures that formulators can follow to make the process go smoother. The earlier a formulator can be involved in the product design phase the better. The formulator can have input into all factors of the delivery system that is being designed to meet customer requirements. These factors range from tablet size and shape to specifications of materials, the cost of final formulation and specifications of finished product. In addition, the formulator should always run multiple prototype batches to test the robustness of the tablet formulation under changing material characteristics, varying environmental conditions and operator variability. A pilot scale batch prior to full production is a must to validate prototype findings and provide a controlled hand-off and training environment for the production operators.

The New Tablet Rainbow

Time was a tablet was limited to the color of its ingredients, which is a pretty neutral palette in the case of most vitamins and minerals. As a result, most tablets looked pretty ordinary, making it harder for consumers to get excited about taking their daily supplements. Botanicals tended to offer a greater array of color, but were still primarily Earth toned. Today, new technologies and tableting products are opening up a new era of color possibilities, pleasing both marketing managers and consumers alike.

Rose Olcese, product manager of cosmetic pigments for EMD Chemicals, said the company’s Candurin® effect pigments can be added to coatings systems to impart a unique pearle-sence appearance to tablets. “In combination with other colorants, the manufacturer can create an appearance that enhances their brand recognition,” she noted. “Making a visual statement on your tablet discourages medication error by the end user, as the tablet will look noticeably different from other tablets a person may be taking.”

The pearly, colorful resulting tablet may protect the integrity of tablets in a marketplace of knock-offs and fakes. “In addition, use of Candurin pigments to enhance a brand name and tablet appearance makes counterfeiting of those tablets that much harder to accomplish,” Ocelse said.

According to EMD, the pigments are added to the coating a tablet-maker already uses and requires no special conditions, processing or quality control. As for quality, EMD produces 15 in four different color groups—silver-white, interference colors, gold, as well as diverse shades of red, brown and orange based on iron oxide—in adherence to GMP (good manufacturing practice) standards, as they are offered for both pharmaceutical and dietary supplement applications.