Research on novel oral controlled release delivery systems focuses on increasing gastric retention or gastro-intestinal absorption. Currently, retention time is quite variable and depends on the individual. Gastric platforms have been developed that adhere to the stomach wall, thereby increasing gastric residence time and allowing for prolonged duration of therapy.
The controlled delivery of macromolecular drugs represents one of the greatest challenges in drug delivery. Transmucosal delivery across the tissues of the oral cavity is an attractive means for non-invasively administering such drugs.
Oral transmucosal (OTM) administration offers several advantages for controlled drug delivery. Viz. bypass hepatic first pass effect. The oral mucosa can be generally divided into two categories: Keratinized tissues (gingiva and palate) and non-keratinized epithelial tissues (sublingual & buccal). The non-keratinized oral mucosa is highly permeable and blood flow to the oral mucosa is exceptionally high.
In addition, an oral mucosal tissue is readily accessible and localization of dosage form with a defined surface area over extended periods should maximize absorption and provide higher degree of control and reproducibility relative to other mucosal delivery routes. These factors combined with the relatively rugged nature of the oral mucosa to physical and chemical injury make OTM an attractive mode for macromolecular drug administration.
One example of OTM based DDS is a bilayered tablet, which consists of a biocompatible adhesive layer that adheres to the gingiva and an active layer containing drug and optionally a tissue permeation enhancer. The active layer contacts the inner surface of the upper lip opposite the gingival application site and delivers the drug as the entire tablet dissolves.
The choice of formulation components of the adhesive and active layers of the OTM system is dependent on the desired release characteristics of the active compound, dissolution time can be varied based on the physicochemical properties of the drug and the profile desired by the glucagon-like peptide (GLP-1) containing tablet for NIDDM therapy.
Potentially therapeutic plasma levels of GLP-1 were achieved after administration of a single OTM tablet in type 2 diabetic patients. The peptide had marked glucose lowering effect during the first two hours. The bioavailability of GLP-1 after oral transmucosal administration was estimated as 47% relative to subcutaneous administration.