NYSCC

Desperately Seeking Synergy…Part I of II

By Joseph Albanese

Synergy. It seems everybody likes to use the word synergy. Look, I’ve already used it three times - and, I’m just getting started.

Synergy is a word that bombards us in our culture nearly every day. Flip through the cable TV channels and you may catch a Wall Street broker talking about the synergy created by the merger of two companies or, a medical researcher making a statement like “The combination of smoking cigarettes and exposure to radon works synergistically to increase the risk of developing lung cancer.” On and on it goes. Rock bands, products and companies are named Synergy this or Synergy that. Check out this news item found on the CNN website:

Modern day Wright brothers
Monday, December 15, 2003 Posted: 12:26 PM EST (1726 GMT)
(CNN) -- Wilbur and Orville Wright were the first to use sibling synergy to slip the surly bonds -- but not the last. Miles O'Brien catches up with two brothers who made an amazing aviation record a reality in their own private Kitty Hawk -- the high desert of Southern California. They're Burt and Dick Rutan - the former a brilliant designer, the latter a man with a velvet arm.

In the Personal Care Industry, raw material suppliers and their customers too (come on admit it) are certainly not excluded from the list of professionals who suffer from the apparent overuse of the word.

Usually I do not care about the precise use of the word synergy in our everyday language. Unless I am either gainfully employed by one of the companies or a serious investor, I would not question the broker’s statement. Likewise, I would simply give the researcher the benefit of the doubt, avoid cigarette smoking, and check the house for radon leaks. Why take chances with one’s health? Tales of siblings working in harmony are always heartwarming and who doesn’t love the alliteration inherent in the words “sibling synergy to slip the surly bonds”.

However, I do care about how we use the word in our industry because it is an important part of our lexicon. Therefore, the misuse of the word in our ingredient and formulation research, whether intentional or not, has become my pet peeve. I must confess I am leery every time someone evokes the word in this context. I closely consider claims of synergy with a critical eye and, (okay) sometimes with a cynical bent. I do not want its overuse to trivialize or its misuse to compromise the meaning of the word until all that remains is a trite buzzword. After all, true synergy, like true love is hard to find. Let us not abuse it.

It is my hope that this article will enlighten and help you understand my point of view. After all, misery loves company. I do not want to be the only one with this particular sort of obsessive-compulsive behavior.

Actually, I know I am not completely alone in this matter. In his article “Measuring Synergy” David Steinberg seems perturbed by the inconsistent manner in which microbiologists input data into the Kull Equation to support a synergy claim on cosmetic preservation. Apparently, this is his particular version of the same basic pet peeve. I feel his pain.

All joking aside, understanding the proper approach to seeking favorable ingredient interactions in cosmetic formulations and how to critically assess/interpret data from mixture experiments will prevent you from making or accepting false claims of synergy.

So, what exactly is Synergy?
First, one must concede that the precise meaning of the word synergy will vary subtly, if not significantly, depending upon the context in which we find it. Many times, we use the word in a way that gives it no more meaning than “combined action.” When used this way it does not convey the full meaning of the word and can be misleading. Synergy always should imply an interaction of two or more factors that produces a better than expected desirable end-benefit. In this specific case, these factors are the components in a mixture (a.k.a. the ingredients in a formulation).

As defined by the inventor Buckminster Fuller who first popularized the word in his book SYNERGETICS “Synergy means behavior of whole systems unpredicted by the behavior of their parts taken separately.” In addition, he adds, “Synergy means behavior of integral, aggregate, whole systems unpredicted by behaviors of any of their components or subassemblies of their components taken separately from the whole.”

Nearly everyone accepts that synergy means, or implies, that the sum measure of something is greater than the expected sum of its component parts. It is more than an additive effect and its antithesis is antagonism. Mathematically:

1 + 1 = 2 is an additive effect.
1 + 1 > 2 is a synergistic effect.
1 + 1 < 2 is an antagonistic effect.

One way Fuller demonstrates synergy is to show how two triangles can join to form four – a tetrahedron. I dare you to read the book for a full explanation. It is a real mind-bender.

Figure 1

How do you know if you have it?
There are various approaches for identifying synergistic interactions depending upon the field of research. Two ways are the ‘Beta (β) Parameter’ used by scientists looking for synergistic interactions between surfactant blends and the ‘Kull Equation’ used by microbiologists (and other disciplines) to calculate the ‘Synergy Index’. In the paper “What is Synergy?” printed in the Pharmacological Review researcher/author M.C. Berenbaum uses an Isobole Method to determine if drugs are interacting together in a beneficial way (synergy – when the dosage required to achieve the desired effect is reduced to a concentration below what can be predicted) or against one another (antagonism). The preferred way for finding and/or verifying synergistic interactions between ingredients in a personal care formulation is the approach of John A. Cornell for mixture optimization that will be covered in Part II of this article.

Figure 2 - Simplified Isobologram

One simply cannot support a true synergy claim in formulation optimization unless the following definition is satisfied:

“In a controlled mixture, a synergistic interaction indicates that the combined effect of two or more ingredients, at a given concentration, is greater than the sum of the contribution from each individual ingredient.”

The essential constraint inherent in the definition is that for every experimental batch the relative proportions of the ingredients under investigation must always sum to unity (1 or 100%). There is a second more common sense constraint for formulations. It is that, for obvious reasons, the ingredient proportions must sum to, greater than or equal to zero. After all, an ingredient obviously cannot be present at a negative level.

Think for a moment about the following data presented in GRAPH 1 published to support a supplier’s claim for their ingredient combined with another to produce a synergistic effect on thickening.

GRAPH 1

In the article, the authors define synergy as “a rheological response from the combination that is greater than that from the sum of the effects of the individual components.” Fair enough, but here is what they say GRAPH 1 shows –

“The aqueous mixture of 0.2% Thickener B and 0.2% Thickener A developed a viscosity of 4,600 cps while the 0.2% solution of Thickener A alone was only 1770 cps and Thickener B alone about 1 cps. Thus, the combination produced almost three times the sum of the viscosities of the individual components, which is significant synergism. Similar viscosity synergism was observed when the concentration of each compound was 0.1%. It therefore appears that the hypothesized interpenetrating network of Thickener A polymer chains and Thickener B colloidal platelets does, in fact, develop to produce the observed synergism.”

In your opinion do you agree with them that this data supports a claim of synergy; i.e. does it fit the definition just provided?

I think not. In this case, the authors disprove their synergy claim with their very own data. While the numbers for A + B always appear significantly higher than A or B separately one must be cautioned that the actual use-level is being doubled form 0.1% to 0.2%. Thus, the supplier is not being faithful to the “at a given concentration” constraint, which is required to satisfy the definition.

Even though 270 cps is certainly much higher than what could be predicted from the sum of its component parts (90 + 1 = 91 cps) it is much less than what can be obtained by using 0.2% of Thickener A alone (1770 cps). The fact that the viscosity achieved by Thickener A alone more then doubles (from 90 to 1770 cps) when its use-level is doubled (from 0.1% to 0.2%) suggests a non-linear effect. The contribution from Thickener B, the material that the supplier is trying to promote/sell, is negligible in either case. Actually, as I will show in more detail later, Thickener B has an antagonistic effect on viscosity. At 0.2% total solids, the 50/50 ratio of Thickener A + Thickener B is only 270 cps. That is actually about 85% less viscous than 0.2% of Thickener A by itself. Nevertheless, the vendor is claiming the viscosity of the combination is “three times the sum” and thus represents a “significant synergy”. I hope it is clear by now that this is insufficient proof. In order to even consider the possible synergy of 0.2% Thickener A combined with 0.2% Thickener B (4600 cps) one needs to know what the viscosity of 0.4% Thickener A and 0.4% Thickener B are by themselves. The researchers simply do not provide us with that data.

……TO BE CONTINUED IN THE MAY 2005 ISSUE OF COSMETISCOPE

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