Formulating for EfficacyTM Copyright © 2014 ACT Solutions Corp. All rights reserved.

Why Formulate for Efficacy? Actives are expensive Claims substantiation is expensive Advertising is expensive Litigation is expensive Getting new customers is expensive Developing new products is expensive

Standard formulation design process Clinical testing Stable base Concentration Model activity Intrinsic activity

How to increase skin delivery? K = Partition coefficient (of active between formulation and skin) The math bit… D = Diffusion coefficient (of active into skin) L= Path length (of active through skin) Ficks’ 1st Law (~rate of active penetrating into skin): J is from Ficks first law, for penetrant going through membrane. Two key things we can affect: 1) Initial concentration in formulation – flux is increased when this is increased 2) Partition coefficient K: in order to get active into skin, it must penetrate from formulation into stratum corneum, controlled by K, ratio of maximum solubilities. Therefore, the quantity of molecules penetrating into the stratum corneum can be increased by increasing the solubility of the penetrating molecule in the stratum corneum or by reducing its solubility in the formulation. Rate of active penetrating into skin can be increased by maximizing the initial amount in the formulation

Categories of actives Insoluble Oil soluble/low polarity Sparingly water soluble Freely water soluble

Hansen solubility parameters Solvency predictions Dispersion forces van der Waals forces Polar forces Dipolar intermolecular forces Hydrogen bonding forces Electromagnetic attractive interactions

Assessing other challenges to delivery posed by actives Size MolV (Molar Volume) Difference in polarity with Stratum Corneum ASG (Active Skin Gap)

Franz Diffusion Cell Data 3.5 fold increase 5 10 15 Formulation not optimised for delivery Delivery optimised formulation Dioic Acid Delivery ( μ g/cm 2 ) Tapes Stratum Corneum Receptor fluid

Formulating for Efficacy™ Approach Intrinsic activity Model activity Assess properties Evaluate challenges Design active phase for solubility and driving force

Dynamics of product on the skin Application Evaporation Permeation

Impact of the Emulsifier Stability (OK, that’s obvious) Aesthetics (yes, but how much?) Delivery (where does it fit with such approaches as Formulating for Efficacy™ ?)

Wiechers study shows that emulsifier selection controls: 74% of overall aesthetic quality of an emulsion Nearly 100% of Appearance, Pick-up, and Rub-out characteristics MESSAGE: Change emulsifier to change aesthetics Use emollient variation to adjust After-feel

Emulsion Stabilization Mechanisms Steric Charge Pickering Polymer Liquid crystalline

Adaptive Approach to Aesthetic Design Emulsifier Appearance, Pick-up, Rub-out Test with target audience Emollient Adjusting After-feel

Driving Development Water, Polar Carriers and Humectants, Actives, Polymers Emulsifiers Emollients, Actives, Waxes

Enlightened Formulation Wheel Actives Emulsifiers Polar carriers, humectants Emollients Fragrance Preservative Polymers and waxes

Further formulation design Design emulsion for aesthetics Design emulsion for delivery Test with target audience Clinical trials Success !!

Contact information Mark Chandler President, ACT Solutions Corp Research Instructor, Univ. of Toledo Office: 302.525.8110 Mobile: 302.559.1594   Mark@ACTSolutionsCorp.com www.ACTSolutionsCorp.com www.FormulatingForEfficacy.com 550 S. College Ave., Suite 110 Newark, DE 19713