The oral mucosa has an intermediate permeability between the intestinal mucosa’s permeability and the skin’s permeability. Depending on the molecule under consideration, the permeability through the oral mucosa can be between 4 to 4000 times higher than in the skin. 

To these differences must be added two other factors that improve the bioavailability of the administered drug. The high blood flow that rapidly entrains the drug, maintaining a high concentration difference across the barrier imposed by the oral mucosa and first-pass metabolism is also avoided.

OTFs are typically water-based, soluble polymers designed to rapidly and consistently deliver drugs. They are placed on or under the tongue and are immediately absorbed by the oral mucosa and the active ingredient is transported directly into the bloodstream.

The first OTF prescribed was Zuplenz (Ondansetron HCl, 4-8 mg) and was approved in 2010. Suboxon (buprenorphine and naloxan) quickly followed as the second approved.

Depending on the drug candidate and the specific indication, OTF can be formulated as:

• Orodispersible film that works like conventional tablets. In this case, the OTF dissolves in seconds in the mouth and the drug substance is swallowed together with saliva and follows the same path as a tablet.
• Transmucosal film in which the active ingredient enters directly into the systemic circulation through the buccal mucosa, avoiding the effect of the first hepatic pass.

Advantages and limitations

OTFs have many advantages over other solid dosage forms, including flexibility and increased API efficacy. For geriatric and pediatric patients, who have difficulty chewing or swallowing solid dosage forms and refuse to take these dosage forms for fear of choking, OTFs are a preferable alternative. Rapid dissolution/disintegration of OTF drug delivery systems is a preferable alternative in patients with a fear of choking. When placed on the tongue, OTFs are immediately moistened with saliva. As a result, they dissolve to release the drug for systemic and/or local absorption.

However, this pharmaceutical form has some limitations.

• Not suitable for medications that cause oral pH irritation and are not long-lasting.
• It is hygroscopic by nature. For this reason, it causes difficulties for long-term protection.
• Requires special equipment for packaging.