FORMULATION

Many potentially very productive bioactives are water soluble, which sounds on the surface to be a good thing.  Sadly, when they are in aqueous solution and applied to the surface of the skin, the potential is unrealized. Within 20 minutes after application to the skin, most of the water in a formulation has evaporated, leaving the active to fall out of solution.  The skin surface barrier, the stratum corneum, is net hydrophobic and thus built to keep such water-soluble materials away. Two large problems to overcome.

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One of the basic tenets of active delivery is that solids diffuse 10,000 more slowly than liquids into the skin.  This is not a problem for a water-soluble bioactive until it is applied to the warm hydrophobic skin surface and the water immediately starts to vacate the premises and enter the surrounding atmosphere. What the formulator needs to find is a suitable solvent that is less volatile, cosmetically elegant, and socially acceptable to the tender sensibilities of the consumer. Since there is no (other) universal solvent, the search is on.

The Formulating for Efficacy™ Software tool uses Hansen Solubility Parameters to predict solubility of bioactives various potential solvents. With an upgrade to the algorithm made several years ago, the prediction accuracy has improved greatly for water soluble and other more polar materials. A project was undertaken to evaluate a number of ‘polar bears’ in the software to determine whether suitable mates could be found for such ingredients as:

Allantoin 

(skin smoothness and wound healing) 

Ascorbic Acid 

(free radical damage protection, skin lightening) 

Betaine 

(osmoprotection, anti-inflammatory) 

Dihydroxyacetone 

(self-tanning) 

Ensulizole 

(UVB absorber active) 

Ferulic Acid 

(antioxidant, wrinkle reduction) 

Kojic Acid 

(skin lightening) 

Niacinamide 

(anti-inflammatory, skin lightening, oxidative stress protection) 

Salicylic Acid 

(anti-acne active) 

Solvent candidates were evaluated, most with good standing with consumers, including:

The Hansen Solubility Parameters of the bioactives and the solvent candidates were derived by the software by inputting the SMILES (Simplified Molecular Input Line Entry System), a linear expression of the chemical structure, into the Formulating for Efficacy Software.

PEG-8 

(ISG – 7.18) 

Hexylene Glycol 

(ISG – 8.92) 

Propylene Glycol 

(ISG – 9.96) 

Caprylyl Glycol 

(ISG – 10.28) 

Hexanediol 

(ISG – 11.52) 

Propanediol 

(ISG – 11.72) 

Glycerin 

(ISG – 11.93) 

Butylene Glycol 

(ISG – 17.39) 

Dipropylene Glycol 

(ISG – 17.55) 

Polyglycerin-10 

(ISG – 108) 

Step number one in management of bioactives is finding that suitable solvent. Percent solubility of the bioactives in each of the solvent candidates was predicted by the software. For Allantoin, Betaine, Dihydroxyacetone (tied with several others), Ensulizole, Kojic Acid, and Niacinamide, Propanediol was the top solvent. For Ascorbic Acid, Glycerin was tops (Propanediol second). With Ferulic Acid and Salicylic Acid, Butylene Glycol and Hexylene Glycol were the materials showing highest solvency. Having high solvency allows for formulation flexibility.

Also, when evaluating potential carriers for bioactives, consideration should be taken to assess the polarity of the solvent in relation to the polarity of the stratum corneum. This is especially relevant because water soluble and other polar bioactives inherently have Hansen Solubility Parameters (polarities) which are a great distance from the polarity of the skin barrier. For effective formulation of such bioactives, a ‘polarity bridge’ can be built between the bioactive and the barrier by selecting an effective solvent that has a lower difference in polarity. This is expressed in the Formulating for Efficacy Software as the Ingredient Skin Gap (ISG.)  When evaluating the table of potential solvents above, the first group of 5 with the lowest ISG’s are generally petroleum derived and cause concerns with consumers. Of the second group, most of which can be obtained in biobased form, Propanediol has the lowest ISG.

An updated formulating approach with water soluble and other polar bioactives has been to introduce enough nonvolatile solvent/humectant carrier such that when the formulation water evaporates on the skin the carrier can handle the full load of the bioactive concentration. An even newer concept is to forget the water entirely and work just with the bioactive and the carrier. This not only solves the issue of running up against maximum solubility for certain bioactives, but also addresses any issues related to instability of a bioactive in aqueous solution. Excellent candidates for such an approach include Ascorbic Acid, Dihydroxyacetone, Ferulic Acid, and Niacinamide. This approach also allows for the use of such carriers as Propanediol that has marketing appeal and a low ISG which may not have enough solvency for a specific bioactive when used at normal levels in an emulsion, but more than sufficient when the system is anhydrous. Beautiful clear serums can be developed which offer superior delivery and efficacy potential. The Diffusion Modeler within the Formulating for Efficacy Software bears this out.

Ensulizole is entirely underutilized as a sunscreen active. When neutralized, it is fully water soluble, feels great (non-greasy, obviously), and provides good UVB protection. Quite possibly it is not more widely used is that this UVB protection is not normally realized because formulation water would evaporate on the skin leaving the active to drop out of solution on the skin just as the light source is activated.  It turns out that an anhydrous solution of Ensulizole does not provide the same sun protection as when in water but introducing a high level of a nonvolatile solvent humectant like Propanediol into an Ensulizole-containing sunscreen significantly reduces the volatility of the formulation water and provides a secondary solvent when the water finally starts to leave. Using the US-maximum 4% Ensulizole, a 25% level of Propanediol, 10% Zinc Oxide, and a porous spherical silica, a great-feeling oil-free low-whitening in-vitro SPF 70+ has been developed.

Another category where water is a willing partner is in cleansing products. For formulation of clear cleansing systems, introducing superior solvents can be very important for efficacy and visual appeal. Building clear moisturizing anti-acne cleansing formulations is made much easier with the addition of such solvents when formulating with Salicylic Acid (difficult to dissolve) and Betaine (freely water soluble but could use help with sticking to the skin). For further development may be an anhydrous humectant solvent-based system. An interesting feature of such solvents as Propanediol is that when applied to wet skin, there is a mild comfortable warming effect.

Formulators of water-soluble and other polar bioactives would do well to look at the specific material and either use a modeling tool or the old-fashioned way to assess the solubility.  No solubility, no delivery. Once solubility is tackled, the view should be shifted to building a polarity bridge for maximizing delivery. Going anhydrous opens up new opportunities for performance, stability, and consumer delight. Working without water – Why not?

MARK CHANDLER        

ACT Solutions Corp. | United States