Dispelling the 'Law of Wiechers' and Maximizing Actives Delivery

By: Johann W. Wiechers, PhD, JW Solutions

Posted: December 16, 2010

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Hadgraft is right, as he probably has been every time for the last 40 years when talking about skin delivery. A formulator can create a 10% formulation that does not work and an 0.1% formulation that does—it depends on the solubility of the active ingredient in a formulation. The formulator should always formulate close to the maximal solubility of the active ingredient in their formulation. This is when the formulator has the maximum driving force for diffusion, or as the skin delivery scientist likes to call it, maximal thermodynamic activity.

A formulator can make a 3% solution of an active in solvent X where the maximum solubility is 3.3%, and another of 2% in solvent Y where the maximum solubility is 2.2% and the skin delivery will be the same. If this is an emulsion and the molecule is lipid-soluble, the formulator can reduce the oil phase, keeping the concentration the same without losing skin delivery since the percentage of maximum solubility is not changed.

How do suppliers know that the maximum solubility of their active in a formulation is always just above 3%? They do not; therefore, any in-use level recommendation cannot be used. It may be 3% for some specific systems, but other systems can easily be created in which the maximum solubility is lower, thereby reducing the concentration of the active in the formulation without losing the efficacy.

Hold your breath; it gets worse. Suppliers of cosmetic ingredients are keen on selling a nicely dissolved active that is easier to use, they say, and this is probably true. A formulator can then add the 3% active but what does the supplier use as a solvent? They use something in which the active is soluble but with the addition of that solvent to the formulation, the total solubility of the active in the formulation is increased, which reduces the skin penetration of the active ingredient. In other words, this solvent may indeed be easier for the formulator in the production process but it reduces the skin delivery of the active.

The supplier's answer is often to add more active, which makes the formulator add more solvent. This results in a higher solubility of the active and even less skin delivery. Supplying actives in a good solvent is just as helpful as the recommendation that you need to add 3% to your formulation. Once this science is understood, the ridiculous nature of the "Law of Wiechers" in cosmetics is realized.