The possibility of improving the flux of nimesulide across the buccal mucosa using the drug in the form of a sodium salt was investigated in our study. The salt form may increase to flux across buccal membrane, starting from a suspension; its lower permeation coefficient is compensated by a higher concentration gradient. The salt was inserted into a mucoadhesive tablet for buccal administration. The tablets were designed to prevent the loss of the drug into the saliva by means of a protective layer and placed on the area not in contact with the mucosa. Ten volunteers were used. The in vitro release from mucoadhesive tablets was examined through a porcine buccal mucosa, using a standard Franz cell, modified for present purposes. The advantages of a higher concentration gradient for the flux, related to a higher solubility of the salt, and to a sufficiently high permeation coefficient of the drug, despite the ionized form, could not be completely exploited, because the composition of the formulation destroys the chemical form of the drug.