Supersaturation as a galenic concept for improving the cutaneous bioavailability of drugs in topical therapy

Abstract

The essential force that allows an epicutaneously applied drug to penetrate the skin is mediated by diffusion. The physicochemical properties of the skin tissue at the site of application and the concentration gradient of the dissolved drug between the vehicle and the stratum corneum are decisive here. One way to specifically improve these diffusion conditions is to use supersaturation. This uses the physical principle of the difference between the solubility curve and precipitation curve (Ostwald-Miers range). During the conversion of the application vehicle into the segregation vehicle, supersaturation of the dissolved drug substance in a solvent is achieved by evaporation, e.g., of a solubilizer. In principle, the change in solubility can also be achieved by heating and then cooling a solution. This principle has already been realized in a formulation of a fixed combination of calcipotriol and betamethasone dipropionate, two lipophilic drugs susceptible to hydrolysis, and is available on the market as a spray foam.