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The purpose was to elucidate the mechanism of action of sodium dodecyl sulphate (SDS) on drug dissolution from discs under physiologically relevant conditions. The effect of incorporating SDS (4–30%, w/w) and drug into discs on the dissolution constant and solubility were evaluated for the poorly soluble drugs griseofulvin and felodipine in a biorelevant dissolution medium (BDM). Dissolution constants from dissolution profiles of drug discs with and without SDS were measured using miniaturized rotating disc dissolution. Solid state changes were investigated by X-ray diffraction. Solubility was determined using HPLC-UV. The interaction between micelles in BDM and SDS was investigated by isothermal titration calorimetry and dynamic light scattering. Isothermal titration calorimetry showed that SDS formed mixed micelles with bile salt:phospholipid (BS:PC) micelles in BDM. Dynamic light scattering showed that the addition of SDS made the BS:PC micelles grow up to 2.5 times in volume. As a function of SDS addition, the dissolution constant showed an apparent exponential increase, while drug solubility showed a weak linear dependence. The pronounced effect on dissolution constant with SDS in the discs is not caused by an increased surface area as SDS dissolves, micelles in the bulk medium or changes in the solid state properties of the drugs. The proposed mechanism involves a high local concentration of SDS at the solid–liquid interface as SDS dissolves and this solubilizes the drug. The improved solubility at the solid–liquid interface provided a much steeper concentration gradient resulted in a faster dissolution. The total amount of SDS in the discs only gave a minor increase in total surfactant concentration in the dissolution medium and did therefore not to any large extent affect the drug solubility in the bulk.