Compositions containing a drug to be delivered and at least one chemical permeation enhancer (CPE), and methods of making and using these compositions are described herein. In a preferred embodiment, the compositions contain two or more CPEs which behave in synergy to increase the permeability of the epithelium, while providing an acceptably low level of cytotoxicity to the cells. The concentration of the one or more CPEs is selected to provide the greatest amount of overall potential (OP). Additionally, the CPEs are selected based on the treatment. CPEs that behave primarily by transcellular transport are preferred for delivering drugs into epithelial cells. CPEs that behave primarily by paracellular transport are preferred for delivering drugs through epithelial cells. Also provided herein are mucoadhesive oral dosage forms. In a preferred embodiment, the oral dosage form is a multi-compartmental device, containing (i) a supporting compartment, (ii) drug compartment and (iii) mucoadhesive compartment.
