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Ketorolac tromethamine, the non-steroidal anti-inflammatory drug, was formulated into mucoadhesive films to overcome the limitations in the currently available dosage and routes of administration which in sequence will increase patients’ compliance. Films were cast from organic and aqueous solvents using various bioadhesive polymers namely: HPMC E-15, Eudragit RLPO, Eudragit RSPO, Carbopol 934P. The prepared films were subjected to investigation for their physical and mechanical properties, swelling behaviors, in vitro bioadhesion, drug permeation via bovine buccal mucosa, and in vitro drug release. These properties were found to vary significantly depending on the preparation methods, the type of the polymers, and the ratio of addition of both plasticizers (i.e. polyethylene glycol and film forming agent. Formulation F4 is selected for best formulation because it shows the 98.85% drug release at time 6 hr. In addition, this film was subjected to in vitro and in vivo release. The obtained results indicate that the concentration of ketorolac in the oral cavity was maintained above 4.0 µg/ml for a period of at least 6 h. This film shows promising results for using the ketorolac mucoadhesive route of administration topically and systemically, and thus it will be subjected to clinical evaluation in future work.