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Well known mucoadhesive polymers such as Carbopol 974P and Pharmacoat 606 and three different mucosas (sublingual, oesophageal and duodenal bovine) were used to verify how the mucoadhesive properties of materials may depend on the mucosa characteristics and if a polymer may reveal more mucoadhesive than another and vice versa by changing the type of interacting mucosa. So, tablets of Carbopol 974P and Pharmacoat 606 were prepared and their mucoadhesion on the three mucosas was set in terms of maximum load and work of detachment, using a texture analyzer. At the same time, mucosas were characterized by immunohistochemical techniques and lectin histochemistry. Results obtained from the Tensile test analyses show that the adhesive power of the two polymers is different in the three mucosas. Particularly, in the sublingual mucosa, Carbopol was more mucoadhesive than Pharmacoat. On the contrary, Pharmacoat was more mucoadhesive than Carbopol in duodenal mucosa. The significantly different behavior of polymers was correlated with the desquamation layer thickness and the differential sialic acid and fucose exposition in the targeted mucosas.