FORMULATING
When you have selected an active ingredient for the desired effect, such as for skin lightening, the emollient system is chosen so as to provide solubility, if it is an oil soluble ingredient such as ascorbyl tetraisopalmitate, or to provide sensory attributes, if it is a water soluble ingredient such as ascorbic acid or the newer peptides. I will also refer you to ‘Formulating for Efficacy’ which is outlined in a later section of this paper. If the drug is poorly soluble in water or oil (eg. Sabiwhite from Sabinsa) then the emollient phase also has the requirement to aid in suspension of the drug to keep it, firstly, to keep it suspended in a stable product, and secondly, to prevent agglomeration.
Emulsion type
While this seems to be of minor importance, some specific conditions exist. It has been found that for hydrophilic drugs increased absorption is achieved from very stable water-in-oil emulsions, provided the internal phase has very small micellar structure. This is probably due to the ionic nature of the drug being shielded from the ionic character of the surfactants in the intercellular channel thereby reducing the tendency for the drug to be trapped in the stratum corneum. It also assists when the drug must pass through the lipid layers deeper in the skin. For lipophilic active ingredients, very stable water-in-oil emulsions seem to be better for sunscreens in that they stay on the surface and do not penetrate readily. More unstable water-in-oil emulsions are better in aiding penetration. For oil-in-water emulsions, the stability (as mentioned earlier) plays a more major part with unstable oil-in-water emulsions being better penetrators, particularly where lipophilic active ingredients are used. It is unfortunate that most water-in-oil emulsions are not aesthetically pleasing, being more a ‘greasy’ feel. To overcome this multiple emulsions are used. Water-in- oil-in-water emulsions have the dual benefit of containing a very small micellar structure of a water-in-oil emulsion with the more aesthetically pleasing feel of an aqueous phase as the external phase.
Multiple emulsions are also used where two hydrophilic drugs are required which may be incompatible with each other, e.g., where one is acidic and the other basic or different pHs are required for stability of each. Here one is dissolved in the internal water phase and the other dissolved in the external water phase with the interlaying oil phase protecting one from the other. Nonionic emulsifiers must be used and one generally makes the internal water-in-oil phase very stable with the oil-in-water combination being somewhat less stable.
124 PERSONAL CARE April 2012
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.
Bearberry. Nanotechnology
Nanotechnology is described by the US National Nanotechnology Initiative as the understanding and control of matter at dimensions of roughly 1 to 100 nanometres, where unique phenomena enable novel applications. Essentially, nanotechnology is a branch of science devoted to the design and production of extremely small matter. Due to the small size and special properties of
nanotechnology materials, they have great potential for use in a vast array of therapeutic products.
In addition, these small materials often have physical or chemical properties that are different from those of their larger counterparts. Differences include altered magnetic properties, altered electrical or optical activity, increased structural integrity, and enhanced chemical and biological properties. These differences have the potential to lead to scientific advances. For example, this technology could be used to create new cosmetic formulations and routes of delivery to previously inaccessible sites in the body.
Formulation for efficacy At this point I would refer you to the late Dr Johann Wiechers’ paper titled ‘Formulating for Efficacy’ where he explained how the thermodynamic activity of an active ingredient could be optimised in a cosmetic formulation by the choice of a primary and secondary emollient. The essence of this theory is the fundamental difference between dermal and transdermal delivery and is dependent on the parameter that you need to change to get the desired effect. In transdermal
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.
A few areas of caution with this theory
are that: It applies only to oil soluble active ingredients in oil-in-water emulsions. Water soluble active ingredients, in an oil-in-water emulsion, are readily absorbed from the external phase of the emulsion and no or little assistance is generally required.
The solubility parameters are not available for a majority of active ingredients used in cosmetics.
The active
The original chemical applied to the skin may not be the active intended (e.g. when vitamin B5 is applied to the skin it is not actually vitamin B5 (pantothenic acid) but a precursor to vitamin B5 (D-panthenol) and will only be converted into vitamin B5 when it enters the skin and it reacts with the skins acids. Vitamin A is similar where, because of stability reasons, we add an ester analogue of retinoic acid, retinyl palmitate. Once in the skin there is a metabolic pathway that converts retinyl palmitate into true vitamin A (retinol). Micronisation of the active is also increasing in importance. Again the work being done with sunscreens is a useful tool
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Sten Porse
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