Systemic Drug Delivery via the Buccal Mucosal Route

is perhaps the most preferred by patients and clinicians alike. However, peroral administration of drugs has disadvantages, such as hepatic first-pass metabolism and enzymatic degradation within the gastrointestinal (GI) tract, that prohibit oral administration of certain classes of drugs, especially peptides and proteins. Consequently, other absorptive mucosa are considered as potential sites for drug administration. Transmucosal routes of drug delivery (i.e., the mucosal linings of the nasal, rectal, vaginal, ocular, and oral cavities) offer distinct advantages over peroral administration for systemic effect. These advantages include possible bypass of firstpass effects and avoidance of presystemic elimination within the GI tract. Many research groups (1–3) have investigated the nasal cavity as a site for systemic drug delivery, and the route already has reached commercial status with several drugs, including leutinizing hormone-releasing hormone (LHRH), cyanocobalamin, azelastine hydrochloride, desmopressin acetate, and calcitonin (4–5). However, the potential irritation and the irreversible damage to the ciliary action of the nasal cavity from chronic application of nasal dosage forms make the nasal cavity less attractive for drug delivery. Also, the large intrasubject and intersubject variability in mucus secretion in the nasal mucosa could be a significant factor affecting drug absorption from this site. Even though the rectal, vaginal, and ocular mucosa offer certain advantages, the poor patient acceptability associated with these sites renders them reserved for local applications rather than systemic drug administration. Similar to the nasal route, the oral cavity as a site for drug delivery also has reached commercial status with several drugs, including nitroglycerin as sublingual tablets for angina and fentanyl as a transmucosal buccal device (Actiq, Abbott Laboratories, Abbott Park, IL) for breakthrough cancer pain (6). Furthermore, oral transmucosal drug delivery bypasses first-pass effects in the GI tract and liver and avoids GI side effects. Unlike the nasal cavity, however, drug delivery via the oral cavity is highly acceptable by patients. The mucosa is relatively permeable, has a rich blood supply, is robust, and shows short recovery times after stress or damage (7). Within the oral cavity the two common regions for drug delivery are the sublingual mucosa (area beneath the tongue) and the buccal mucosa (inner lining of the cheeks). Selecting one over the other is mainly based on anatomical and permeability properties of the vari-