The Science behind "Formulating for Efficacy"

A fundamental difference between dermal and transdermal delivery is the parameter that you need to change to get the desired effect. In transdermal drug delivery, pharmaceutical formulators use skin penetration enhancers that enhance the diffusivity of a chemical through the skin. The result is more drug going in faster. Therefore there is less drug in the skin but more drug through the skin. This is, in fact, exactly the opposite of what one would like to achieve in dermal delivery. There, you would like more active ingredient to go into the skin but then to stay there. The way to do this is by increasing the partition coefficient and not the diffusion coefficient.

How does one enhance the partition coefficient of an active ingredient? How does one change the ratio of its concentrations in the stratum corneum and the formulation? A partition coefficient is the ratio of the solubilities of an active ingredient between the stratum corneum and the formulation. Therefore, the partition coefficient can be increased by increasing the solubility of the active ingredient in the stratum corneum (while keeping the concentration in the formulation the same) or by reducing its concentration in the formulation (while keeping the concentration in the stratum corneum the same).

Therefore, one needs to know the solubility of the active ingredient in both formulation and the stratum corneum. Measuring these values is not as easy as it sounds. But the solubilities can be estimated via the Hansen Solubility Parameters. The "Formulating for Efficacy, the Software" program calculates these HSPs of active ingredient, the formulation in which it is incorporated and the stratum corneum. The solubility is higher if the HSPs of two chemicals are closer together. Therefore the chemical distance in Hansen space is also calculated and from this, an estimation of the skin delivery can be obtained. The "Formulating for Efficacy, the Software" computer program calculates the solubility of the active in millions of combinations of emollients. Depending on what you asked for (to solubilized as much active as possible in your formula, or to increase the partitioning of your active into the skin, or to reach a specific maximum solubility in your formulation), the computer program provides you with the most suitable formulation compositions.

A demonstration of the program can be seen by clicking here [1].