2002 ANNUAL SCIENTIFIC SEMINAR 293 TARGETED PENETRATION AND RELEASE OF ASCORBIC ACID BY THE USE OF MULTIPLE PIASE TECHNOLOGY Gerd H. Dahms, Ph.D., Holger Seidel, Ph.D., and Andreas H. Jung, Ph.D. IFAC GmbH & Company KG (Institute of Colloidtechnology), Duisburg, Germany Multiphase polyol-in-oil-in-water (POW) emulsions belong to the family of mt•ltiple emulsions. Unlike the well known water-in-oil-in-water (WOW) emulsions, which consist of a water-in-oil (WO) emulsion dispersed in a given water phase, a multiphase POW emulsion is a complex system in which a conventional oil-in-water (OW) emulsion is in competition with a polyol-in-oil (PO) emulsion dispersed in it. Since the PO emulsion is the core element of the multiphase POW emulsion, we would now like to take a closer look at this type of emulsion. PO emulsions The structure of PO emulsions is similar to that of the well known WO emulsions with the difference that polyols, instead of water, are dispersed in a given oil phase. A question that certainly arises at this point is: what are the advantages of PO emulsions as opposed to WO emulsions. One answer to this question, among others, is the different solvent behavior of polyols and water. The amphiphilic solvent properties of polyols enable them to dissolve both hydrophilic and lipophilic substances. Furthermore, they are able to dissolve substances, such as polyphenols, which are not soluble in either water or oils. In addition, polyols protect active substances which are sensitive to hydrolysis, e.g. ascorbic acid, urea or enzymes, against chemical decomposition. Another favorable characteristic of PO emulsions, apart from their amphiphilic solvent properties, is the extremely small extent to which they dissolve atmospheric oxygen. As a result, easily oxidized active substances can be afforded excellent protection against oxidative decomposition by dissolving them in polyols. Because of their outstanding properties, PO emulsions offer an interesting alternative to WO emulsions. PO emulsions worked into OW emulsions offer an ideal vehicle for the stable encapsulation of active substances. Active substances dissolved in the polyol phase of a multiphase POW emulsion can be protected in this way against oxidation and hydrolyric breakdown. This presupposes, hoxvever, that the active substances do not travel from the polyol phase into the external water phase via diffusion and that any oxidative attack from the outside is xvarded off successfully. Protective measures against oxidation The amount of protection against oxidative attack conferred on the active substances dissolved in the PO emulsion depends solely on whether oxygen penetrates the polyol phase. For example, oxygen radicals can be transported into the polyol phase via the oil phase of the PO emulsion or via the water phase of the OW emulsion. The possibilities for oxygen radicals to penetrate the polyol phase via the oil phase can be reduced fairly simply by using only inert oils, e.g. silicone oil or isoparaffin oil, in the PO emulsmn. Oils of this kind can neither be attacked by oxygen - and thus form oxygen radicals in the oil phase - nor transport oxygen. In addition to using inert oils in the PO emulsions, further measures should be taken during the formulation of POW emulsions to lessen the formation of oxygen radicals. In particular, it is very important to protect the water phase. Owing to the relatively high solubility of oxygen in water, oxygen radicals can be created repeatedly in the aqueous phase of an OW emulsion. If highly concentrated PO emulsions are used, the oxygen radicals created in the water phase can gain access to the polyol phase via interfacial membranes. If the polyol droplets are separated from each other by a sufficiently thick oil layer as a result of the low polyol concentration, however, the diffusion of oxygen radicals will be suppressed. It is advisable in any case, however, to add a free- radical trap to the water phase. Diffusion of water-soluble active substances Up to this point we have been discussing the question of how to stabilize the active substances present in encapsulated form in PO emulsions to protect them against oxygen radicals. An issue that still needs to be clarified, however, is how such PO emulsions behave in multiphase multiple POW emulsions with respect to the diffusion of water-soluble active substances from the polyol phase into the water phase. In conformance with the Laxv of Osmosis, the emulsion system attempts to equalize the different osmotic pressure between the polyol phase and the water phase. Depending on the composition of the two phases, water will either diffuse into the polyol phase or active substances and polyols will diffuse into the water phase. The flow triggered by the difference in osmotic pressure can be calculated according to the equation formulated by Florence and Whitehill (I):

294 JOURNAL OF COSMETIC SCIENCE Vo= DwA/fix* An/RT where: V o • volume flow of the diffusing substances diffusion constant of the diffusing substances interface of the multiple droplet Ax = thickness of the oil membrane An = osmotic gradient As can be derived from the above equation, diffusion decreases as the thickness of the oil membrane increases. In other words, the lower the concentration of the dispersed polyol phase in the PO emulsion, the more favorable the Ax values. Since the diffusion of a substance through a medium is a transport phenomenon, it is opposed by the viscosity. As a result, it is beneficial to keep the viscosity of the oil phase as high as possible. An oil membrane with a high viscosity and a layer thickness of 50-100 nm can already present a virtually insurmountable obstacle to diffusing substance. The hypothesis of Florence and Whitehill presumes that all the droplets in a multiple droplet are separated from the phase boundary layer by an oil membrane. However, this is not the case: several polyol droplets lie directly on the edge of the multiple droplet. At this location, the membrane of the dispersed polyol droplets meets the membrane of the multiple droplet. Since in this case Ax -- o, the diffusion rate is determined solely by the viscosity of the interfacial membrane surrounding the polyol droplets. Since this membrane consists of a liquid crystalline cubic and inversely hexagonal phase which exhibits a high viscosity at temperatures of up to = 40 øC, the diffusion through this liquid crystalline membrane is relatively low. However, diffusion out of or into the multiple droplets can be regulated not only via the viscosity of the interfacial membrane or the layer thickness of the oil phase between the interfacial membranes. Instead, it can also be regulated via the coverage of the external interface by multiple droplets. In particular, linear polymers, e.g. xanthan gum or mixtures ofxanthan gum with gum arabic or crosspolymers. Polymers of this kind form fairly viscous interfaces when they adhere to the multiple droplets these interfaces present both a mechanical and steric obstacle to diffusion. Compatibility between OW and PO emulsions In addition to diffusion, however, the competing OW emulsion also poses a threat to the stability of the multiple droplets. The stability of the multiple droplets is endangered, in particular, by short-chain hydrophilic emulsifiers which are able to disengage themselves from the liquid crystalline gel network. To attain stable multiple emulsions, therefore, it is advantageous to employ a balanced mixture of complex emulsifiers. Furthermore, the multiple droplets, by virtue of their size, display a tendency to creaming and, in the worst case, to coalescence. According to Stokes' Law, the mobility of the multiple droplets can be restricted only by an external bulk water phase possessing a sufficient viscosity. V =2 r2gAp/9rl v = droplet velocity r = particle size g = gravitational constant Ap = change in density r 1 = residual shear viscosity Organic polymers, or mixtures of xanthan gum and bentonite, are especially suitable for this purpose. Storage stability of the active substances