Robert Green01.01.02
The Laboratory Notebook
Answering important questions about quality.
By Robert Green
Once again our mailbag is full of great questions. This month’s topics are determining the purity of a raw material after it’s encapsulated with other ingredients, analyzing unfamiliar botanicals and dissolution testing.
Q. I am an experienced formulator and produced a chondroitin sulfate/glucosamine capsule which, when analyzed post-production, was short a significant amount of chondroitin sulfate. The certificate of analysis for the chondroitin sulfate raw material reported a purity of 92%, but I am now convinced that the percentage purity was lower and this caused the shortage. Can you take the capsule and determine what the percentage purity of the raw material was?
A. Sorry, it’s too late. The percentage purity of a raw material generally can only be determined when the raw material is intact and here’s why. No sample of either chondroitin sulfate or glucosamine is 100% pure, since there are impurities in both products. For demonstration purposes let’s say your raw material of chondroitin sulfate and glucosamine is 92% and 98% pure, respectively. This means that the percentage of impurity for chondroitin sulfate and glucosamine is 8% and 2%, respectively. When we test each product independently we know that the percentage of purity and the corresponding impurity relates solely to the individual raw material being tested.
Now we combine the two raw materials in a capsule and we know the capsule will contain the impurity of each component. However, we are unable to attribute the “non-chondroitin sulfate/glucosamine” between the two ingredients. Is the impurity attributable 80% to one and 20% to the other, or is it 50%/50% or any other combination? There is no way to tell. And that’s ignoring the fact that finished capsules usually contain additional ingredients such as flow agents to complicate matters.
However, all may not be lost. As an experienced formulator you probably retained a sample of the chondroitin sulfate raw material so let’s test it to confirm your theory.
There are two lessons to be learned from this story. First, always retain samples of ingredients and finished products. It is an easy (and many times the only) way to go back in time when an issue surfaces. And second, test your raw materials before you commence production. The chondroitin sulfate analysis would have cost you $165, which now looks dirt cheap compared to the loss of a production run that produced a below-grade product. Whether you conduct analytical testing in-house or by an outside lab is your decision, but doing so is not only the right thing to do, it makes good business sense.
Q. I am about to launch a product containing a little-known botanical and to insure product consistency I would like to institute analytical testing of the raw material and finished capsules. I’ve checked with an analytical lab and was told that the botanical is not on its list of tests performed and therefore they could not help me. Does this mean I cannot institute a testing program?
A. Probably not. Like in any business, different analytical labs operate differently. Most labs in the supplement industry maintain a list of products they test; if your product is not on the list then they cannot help you. (There is nothing wrong with this approach since many labs do a good job of analyzing familiar material on the list but lack the expertise or interest to develop new methodologies or simply do not want to devote the necessary time and expense to it.) There are, however, labs with a more scientific bent that are delighted to undertake these projects.
Generally speaking the first step in developing an analytical method for an unfamiliar botanical is to search numerous scientific databases to uncover peer-reviewed literature written on the species. You will need both the Latin and common names to do this. It is very rare to find nothing published about a botanical (that usually means the Latin name is incorrect).
The next step depends upon the amount of work already published on the species. In most cases we find an analytical method has already been published, so we are left with duplicating and validating it. In those situations where no analytical method exists the job is much harder, since we now must devise one. How difficult this job is again depends upon the state of the peer-reviewed literature. If the literature describes the chemical groups contained in the botanical, then we can use that information to determine what components can be the subject of analysis and devise the methodology based on that. If the literature is not that advanced, we must review the botanical’s “first principles,” that is, that group of scientific tests used to originally identify the material. We then apply those first principles to the material to be tested. From there we can create an “analytical standard” of that material for use in future testing. It sounds simple but in actuality requires significant expertise, equipment and effort to do it correctly.
As for costs, if an analytical method appears in the literature there may be no or little cost in addition to the standard analytical fee. If no published method exists we are now talking thousands of dollars.
You will note above the phrase “peer-reviewed literature” was used repeatedly and this was done purposefully. Peer-reviewed literature refers to papers published in peer-reviewed journals (that makes sense). For those journals prior to publication a paper is circulated among experts in the field (“peers”) who review, comment upon and sometimes challenge the paper. Only when the paper passes this rigorous review will it be published. Having met this high standard, these papers then hold great weight. True scientific organizations will only rely on scientific information contained in peer-reviewed publications.
Q. I received a niacin sample that the manufacturer claims eliminates the “niacin flush.” This is accomplished through a special process that causes the niacin to be released slowly over time. Can I confirm this?
A. Yes, it’s called a dissolution test. For some background, it is common to experience a “niacin flush” when taking an unusually high amount of niacin. While this column is not intended to provide medical advice, the flush is a reddening of the skin and/or an itchy feeling caused by a swelling of the blood capillaries. As you can imagine, the flush effect is not desirable and many manufacturers have substituted complex niacin/amide that does not cause the flush. Others have attempted to devise time-released niacin that slow the rate of niacin absorption and thereby lessen or eliminate the flush.
To test a time-released niacin (or any other product for that matter) a dissolution test would be employed. Dissolution refers to a product’s ability to release a specific compound into a medium that simulates the gastrointestinal tract where the product is expected to dissolve. While there are various types of dissolution apparatus, the basic principal is the same: the product is subjected to agitation in a simulated gastric buffer. At specified intervals the solution is then tested for the compound at issue. This then determines if and at what rate the compound is released. The United States Pharmacopeia (USP) has detailed provisions on conducting dissolution testing.
For your purposes you should get the dissolution specifications from the manufacturer. Then conduct a dissolution test and see if there is a correlation. A dissolution test is a relatively easy and inexpensive method to get important information about products, and we see an increasing demand for it.NW