The saturation solubilities of nicotine and scopolamine bases as well as acidic paracetamol were measured in two different model stratum corneum lipid matrices. Light microscopy visualized the presence of drug above its solubility either as droplets or crystalline particles. Neither wide-angle X-ray diffraction nor DSC detected the drugs. The saturation solubilities of the nicotine and scopolamine bases are 3-5% w/w and 5-10% w/w respectively. Paracetamol strongly disrupts the lamellar phase formed by the lipids and could be dissolved to >20% w/w. Based on these results the saturation solubilities of nicotine and scopolamine in an intact stratum corneum membrane are estimated to be up to 17.5 μg and 35 μg drug per milligrams of stratum corneum membrane respectively. These concentrations are well above values obtained by tape stripping of intact stratum corneum during a permeation experiment. The drug's saturation solubility in the stratum corneum's lipid phase is therefore unlikely to be rate-limiting for permeation of these two drugs.
