by Eric Brand

The addition of excipients generally affects the concentration ratio of granules and other delivery forms such as tablets and gelatin capsules. Excipients are used for a variety of purposes, but they are primarily used to improve the consistency of the finished product. Although they have an important role, excipients affect the concentration ratio because they dilute the active extract. The type and quantity of excipient varies depending on the manufacturing method and the delivery form of the finished product.

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Improving Consistency

For loose granules, excipients are necessary because the extract powder will clump together without the addition of substances such as starch or dextrin. Without any excipient, the pure concentrated extract powder (known as qing gao fen) is difficult to work with because it is slightly sticky, very fine, clumps easily, and easily produces dust clouds when agitated. Typically, the granulation process combines the use of excipients with a sieving process to create granule kernels of a uniform size. Excipients thus help to create the right consistency so that the granule powder is easy to work with.

It is possible to avoid the use of excipients if the granules are packaged in single-dose foil packs, but in actual practice most granules packaged in foil packs still contain dextrin or starch as an excipient. Although foil packs are extremely common in mainland China, many practitioners in the West as well as Hong Kong and Taiwan prefer loose granules to individual foil packs because the granules can be easily weighed and mixed together in any proportions needed, and the packaging is more “green.”

Delivery forms such as tablets and “tea pills” require excipients that function as a binder. Typically, pill products contain binders and lubricants such as silica, starch, magnesium stearate, and lactose powder. Tablets and pills can achieve relatively high concentration ratios because they do not require large amounts of excipients, but it is essential to know the relationship of the tablets or tea pills to the raw herbs that created them. In some cases, finely ground, non-concentrated herbs are pressed into a tablet form; buyers must pay attention to concentration ratios when assessing tablet products to ensure that a true extract is being purchased. (Blue Poppy's new tablet line, called caplets because the tablet is capsule-shaped, use only hydrated silica as an excipient. We believe that silica is the most benign excipient available, and our tablets are a 7:1 full-spectrum water extract.)

For products that are encapsulated, the starting material can be either pure extract or extract with starch or dextrin. There is wide variation in what goes into gelatin capsules, because many granule companies simply fill capsules with the same product that is packaged loose in 100g bottles (loose granules require more excipient than the capsule delivery method requires, but it is often not practical for companies to produce separate production lines for their encapsulated products). Regardless of the starting material that is put into gelatin capsules, a small amount of excipient is often added to improve the smooth flow of the powder in the encapsulation machine. (Blue Poppy's encapsulated products do not use any dextrin or starch, pure dried extract is used without any fillers whatsoever. When this extract is encapsulated, a small amount of rice flour is added to improve the flow of the encapsulation machine, but no unnecessary fillers are used.)

Dilution

Relatively high doses are required for most items in Chinese medicine, and excipients are often minimized because they dilute the potency of the product. However, excipients are occasionally added to deliberately dilute the finished product, especially in the case of expensive or toxic substances.

Dilution with excipients is common in pharmaceutical drugs because of the high potency of many synthetic chemicals, but some strong agents in Chinese medicine are also diluted to improve ease of measurement and to reduce the risk of overdose. For example, one key Asian supplier of toxic medicinals in granule form dilutes the dangerous insect medicinal Ban Mao (Mylabris) so that one gram of extract contains the equivalence of only 0.1g of the original substance. This makes the dose easier to measure with a spoon and it reduces the risk of overdose. As with pharmaceutical drugs, transparency in labeling is the only way to truly manage such products effectively.

Some items, such as Gan Cao (Glycyrrhizae Radix) and Fu Zi (Aconiti Radix Lateralis Praeparata) can naturally achieve relatively high concentration ratios but they are often diluted because their typical daily dose is relatively moderate. Thus, while it may be possible to produce highly concentrated extracts of these substances, high concentrations become a nuisance when it comes to measurement. For example, if a 9:1 extract of Gan Cao is made but the majority of users only prescribe the equivalent of 3-6 grams of raw Gan Cao per day, the amount that must be weighed per dose is 0.33-0.66 grams of the 9:1 extract. In this example, diluting the extract to 6:1 makes it more manageable because the daily dose becomes 0.5-1.0g, a far easier number to work with in practice.

As mentioned previously, gelatin items cannot be concentrated. Gelatins are typically diluted when made into a “granule” form, because the gelatin must be mixed with starch, pueraria powder, clamshell powder, or a similar powdery agent that can be baked with the gelatin so that it can be ground. The traditional product E Jiao Zhu (Asini Corii Gelatini Pilula) is a pellet made by baking E Jiao with clamshell powder, and this same principle is in use when granule companies package powdered versions of gelatin products. Without a starch or powder to dilute the gelatin, it cannot be ground to a powder because the heat generated by the friction of grinding will turn the gelatin into a cement-like mass. Thus, gelatin products are often diluted in granule form.

Expensive items are often diluted to make the product appear to offer better value. Many herbs, such as Chuan Bei Mu (Fritillariae Cirrhosae Bulbus), Ren Shen (Ginseng Radix), and Tian Ma (Gastrodiae Rhizoma) are commonly diluted with excipients to reduce “sticker shock” when the customer sees the price of the product. (In the case of Chuan Bei Mu, many suppliers use either a low concentration of “true” Chuan Bei Mu, or a significantly concentrated extract of its close substitute, known as Ping Bei Mu. There is generally full disclosure of this on the Asian market but minimal disclosure on the Western market, because most Western practitioners don’t know the difference and don’t ask.) At present, relatively few companies openly advertise the concentration ratios of their products; there is significant competition to keep prices low and there is little reason to maximize the potency of the extract when a majority of customers do not ask for information on its concentration.

Variability

As mentioned in the section on “Understanding Excipients,” different excipients are prominent in different markets. For example, starch is the most prominent excipient in Taiwan while dextrin is the most prominent excipient in mainland China. Patients in Taiwan prefer to take the powder directly by mouth, and fine granules made with starch are superior for this administration method. Patients in mainland China mix the granules in hot water, so coarse, water-soluble granules made with dextrin are preferred.

In Taiwan, all granule products vary significantly in terms of their concentration ratios. While the items range from just over 1:1 to 17:1 or more, the majority of products in Taiwan come out with about a 3:1 to 5:1 concentration ratio. In Taiwan, most granules are made with about 50% starch as an excipient, though some suppliers use only 35% or so. Although there are a few exceptions, Taiwanese labels typically express the relationship between the raw herbs and the finished product very clearly on the label. Thus, consumers in Taiwan can determine exactly how much raw material is concentrated down to one gram of extract powder.

Interestingly, practitioners in Taiwan rarely prescribe granules based on their concentration ratios and the mathematical relationship of the powder to raw herbs. Rather, Taiwanese practitioners often use granules at a general daily target dose of 18 grams per day or so, because Taiwan’s national insurance only covers doses of 6.0 grams per dose (typically given three times per day to reach a total of 18g/day). Most Taiwanese TCM doctors have extensive experience with granules and they generally combine multiple formulas together. The prescribing style there revolves more around ratios of the different formulas in the total target dose rather than the raw herb equivalence. Because Taiwan uses a different dosing style and a different prescription style when using granules, the idea of using raw herb equivalence as the guideline to granule dosage never gained much traction there.

By contrast, most TCM doctors in mainland China primarily think about raw herb equivalence when prescribing granules. Whole formulas are not combined to the same degree as they are in Taiwan, and there is no single widely used target dosage based on insurance reimbursement. Consequently, the granule prescription style in China largely revolves around a raw herb prescription and its equivalent dosage in a concentrated form.

In mainland China, granules are administered in single-dose foil packs, with each packet containing the concentrated equivalent of a standard daily dose of a given medicinal. The concentration ratio of each product varies dramatically based on the solubility of the substance itself, and the weight of the granules in the pouch varies depending on the concentration ratio and the potency of the medicinal (a low-dose item like licorice would have less powder per pack than a high-dose item like rehmannia, even if the two had the same concentration ratio).

Overseas markets, such as the USA, have a higher demand for loose granules than for single-dose foil packets. Thus, when mainland Chinese granule suppliers produce products for the U.S. market, it is common for the variable concentrations of the original starting granules to be evened out with the addition of more dextrin. Here, dextrin is used to dilute the products that have high concentrations to an even concentration ratio. 5:1 concentrations are the most common, because most single herbs can meet or surpass the 5:1 concentration.

In this situation, the manufacturer bases the concentration ratio on a commercial decision. For consumers that dose granules based on their raw herb equivalence, dealing with multiple concentration ratios is a nuisance. Diluting the stronger items (6:1, 10:1, 8:1, etc) to 5:1 allows for easy dosage calculation, and 5:1 generally works out well for most items.

However, some products, especially rich, oily, sticky substances and items rich in polysaccharides are difficult to concentrate to ratios as high as 5:1. Such items tend to clump together easily and they may lose their integrity and consistency if they are concentrated beyond 3:1 or so. Examples of such medicinals include Gou Qi Zi (Lycii Fructus) and Dang Gui (Angelicae Sinensis Radix). Unfortunately, many suppliers of 5:1 extracts do not disclose that there are exceptions that complicate the relatively neat marketing angle of consistent 5:1 ratios.

At present, lack of disclosure about concentration ratios remains an important issue. Suppliers rarely disclose the quantity of excipients and many suppliers of 5:1 extracts from mainland China do not mention the fact that a few agents are not able to achieve 5:1. Similarly, many Taiwanese suppliers do not disclose the fact that their products vary widely in their concentration ratios. Consumers are generally not well-informed on the regional variations in prescribing styles and the issues that affect concentration ratios, so most consumers like to hear a simple answer like 5:1. Thus, many granule suppliers just state that the products are 5:1, even if they are not.

In an effort to solve these problems, more and more suppliers are beginning to clearly state the concentration ratios of their products. Some innovative companies have even taken to creating multiple tiers of concentration ratios for their products: items with high concentration ratios are done at a 9:1 concentration, items with medium concentrations are done at 6:1, and items that cannot be concentrated that high are done at 3:1. Such an approach provides a good balance, because it allows for open disclosure, minimal excipients, and ratios that are flexible enough to reflect the complex reality of single herb extracts and their potential concentration ratios.

It is this latter approach that we are using at Blue Poppy for our upcoming single extract line. For reasons that I will be expanding upon in the next blog in this series, formulas are easy to produce at consistent concentrations (for example, our new caplet line is concentrated at 7:1 across the board). However, single herbs invariably have variation in their potential concentration ratios, which requires a solution like the one outlined above.

Background: Understanding Excipients

Excipients in granules are often called “fillers.” Although the excipient (filler) is indeed an inert substance that dilutes the concentrated extract, the use of excipients is an essential aspect of granule manufacture. Most granules made without excipients clump together rapidly upon exposure to air and humidity, which dramatically affects the shelf life and convenience of the product.

While reducing the quantity of excipients is generally desirable from the perspective of maximizing potency, excipients play an essential role in most granule products. The precise type of excipient used varies depending on the climate and the market preferences within a given region. Additionally, the method of ingestion affects the choice of excipient, since different excipients affect the consistency of the granules themselves.

Excipients in granules perform several important roles. Most importantly, excipients help the extract powder achieve a uniform consistency and prevent the powder from clumping together. The principle excipients used for granules include starch, dextrin, lactose, soluble dietary fiber, and cane sugar (usually only one of the above is used in any given product).

Starch is the most common excipient in Taiwan. Taiwan’s high humidity makes starch an ideal excipient because it doesn’t absorb water as easily as dextrin. In addition, patients in Taiwan typically ingest the powder by pouring it into their mouth rather than mixing it in water. Thus, the Taiwanese market prefers a fine powder that can be poured into the mouth directly without being too sticky, and there is less demand for a completely water-soluble finished product. Large hospitals and clinics tend to use multiple brands of granules simultaneously in Taiwan, so most companies tend to produce finished products that have the consistency of a fine powder (called xi fen) to ensure uniformity when mixing.

By contrast, dextrin is the most common excipient for granules made in mainland China. Dextrin is preferred in the mainland because it is more water-soluble. The use of dextrin tends to make a slightly larger granule, which is more appropriate for use in regions where the granules are taken by dissolving them in hot water. Dextrin is advantageous primarily because it dissolves better than starch, and it can be used in lower quantities so that less inert material is present in the final product. However, dextrin absorbs water more quickly than starch so it is less desirable for use in hot, tropical climates. Dextrin-based products can often achieve higher concentrations than starch-based products, in part because the granules themselves form larger, denser particles. While this is desirable for patients that mix the powder in water, it is not preferred by patients that pour the powder straight into their mouth.

The vast majority of products used by Western practitioners of Chinese medicine use either starch or dextrin as an excipient. Other excipients are far less common on the Western market. For example, lactose is a common excipient in Japan but it is not a preferred excipient for the U.S. market because of fears of lactose intolerance. Similarly, cane sugar is popular for OTC products on the Chinese domestic market, but it is not commonly seen in professional products on the U.S. market. Soluble dietary fiber remains relatively uncommon in granules, although it is widely used outside of the TCM industry.

Finally, crude herb powder has been widely used as an excipient in granules, though its use is now on the decline. Adherents maintain that using the crude herbs as an excipient is preferable to using a wholly inert material, but the use of crude herbs can be problematic in terms of heavy metal and microbial contamination. In the past, the use of crude herbs (or the dried, “spent” herbs recovered following the decoction process) was prominent in Taiwan, but this practice is no longer very popular.