Standardization of Botanical Preparations

Standardization is probably one of the most controversial terms used to describe herbal supplements. Most would agree that the goal of standardizing herbal products is to provide product consistency and thus a reliable health benefit.

However, the term has been defined in several different ways. Standardization can mean the establishment of a consistent biological effect, a consistent chemical profile, or simply a quality assurance program for production and manufacturing.

How the process of standardization is applied depends, in part, on whether the active constituents in the botanical are well established. For that reason, the European Union has defined three categories of botanical products:

  1. Those containing constituents (single compounds or families of compounds) with known and acknowledged therapeutic activity that are deemed solely responsible for the clinical efficacy;
  2. Those containing chemically defined constituents possessing relevant pharmacological properties which are likely to contribute to the clinical efficacy; and
  3. Those in which no constituents have been identified as being responsible for the therapeutic activity (Lang and Stumpf, 1999).

The standardization of active ingredients in botanical preparations is a well-established procedure that has been used for over a century. Before sophisticated chemical analytical methods were available, and when the active principles were unknown, preparations were standardized to biological activity.

This was accomplished with the help of bioassays: measurements of activity in animals or animal tissues. Bioassays were especially important tools for normalizing the activity of powerful drugs, such as digitalis, in which small variances in the glycoside content could lead to sufficient differences in the cardiac stimulating effect that could be dangerous.

Still today, the potency of digitalis preparations is determined using a pigeon assay, which compares the activity of the new preparation to that of a standard preparation (U.S. Pharmacopeia [USP], 2004b).

In those instances in which the chemical constituents deemed responsible for the clinical efficacy (active ingredients or active components) are known and easily measured, chemical analysis can indirectly determine biological activity. With the advent of more sophisticated chemical analytical techniques, it became more efficient to replace bioassays with the measurement of chemical constituents.

Standardization of a botanical product with established active components is achieved by adjusting the preparation to contain a defined level of active substance or group of substances in the dosage form. This can be achieved by adjusting the final amount of raw material (i.e., extract or powdered herb) in the dosage form so as to include a consistent amount of active constituent.

It can also be achieved by including a consistent amount of raw material that contains a consistent amount of active ingredient. In the latter case, the consistency of the raw material is achieved by blending different lots of material. As an example, milk thistle preparations contain silymarin, which is accepted as the active component of the botanical.

So, the amount of product in the dosage form could be either a fixed amount of silymarin in a variable amount of total extract, or a fixed amount of extract that has been adjusted to contain a fixed amount of silymarin. Guidelines for the standardization of specific botanical preparations can be found in pharmacopoeial monographs.

These guidelines include the methods used to determine the levels of active ingredients. As an example, the United States Pharmacopeia defines belladonna extract as containing not less than 1.15 g, and not more than 1.35 g, of alkaloids (measured as atropine [dl-hyoscyamine] and scopolamine via high performance liquid chromatography [HPLC]) in 100 g extract (USP, 2004a).

The European Pharmacopoeia defines standardized belladonna leaf dry extract as containing not less than 0.95 percent, and not more than 1.05 percent, total alkaloids calculated as hyoscyamine measured via titration (European Pharmacopoeia [Ph Eur], 2002a).

An important distinction can be made between single chemical compounds that are active ingredients and active components of a mixture. For example, hyoscyamine as an isolated compound may be an active ingredient in a pharmaceutical formula. However, as a component of belladonna extract, and one of several alkaloids in the extract with activity, it is an active component of the extract.

Standardization to active constituents can ensure consistency between lots produced by the same manufacturer.However, it is just one step toward comparing a proprietary preparation that has been tested in clinical studies with another proprietary preparation of the same botanical.

Even if the claimed level of constituents is accurate, the inherent variability in the undefined portion of the extract must be considered. In addition, different formulations or routes of administration may affect the bioavailability (levels of active components present at the site of action in the body).