Abstract: Methods for treating a patient with ondansetron are described. The method includes administering a solid pharmaceutical composition having ondansetron and a buffer to the patient. Ondansetron is absorbed across a permeable membrane of the patient's oral mucosa. The buffer may include two different buffering agents, such as sodium carbonate and sodium bicarbonate. The buffer may raise the pH of saliva to a pH of between 7.1 to 13. The patient may suffer from emesis, such as nausea and vomiting associated with cancer chemotherapy and radiotherapy.

Abstract: Compositions, methods, and formulations for delivering 5-HT3 antagonists across the oral mucosa are described. In some variations, the described compositions comprise at least one 5-HT3 antagonist, which is at least partly in an ionized form, and a buffer system. The buffer system generally comprises at least two different buffering agents and is capable of changing the pH of saliva from an arbitrary initial pH to a predetermined final pH, and of sustaining the final pH for a period of time. The predetermined final pH favors substantially complete conversion of the ionized form to the un-ionized form. In other variations, the described compositions comprise a 5-HT3 antagonist, at least partly in an un-ionized form, and a buffer system. In these variations, the buffer system is capable of providing an adjusted salival pH such that the 5-HT3 antagonist remains in its un-ionized form. Dissolving tablets are also described.