Physiological Pharmaceutics

Buccal drug delivery 47Figure 3.6 The gingival marginor non-existent, and its base is formed by junctional epithelium, which extends from thebase of the sulcus. The intercellular spaces in the junction epithelium are considerablylarger than in either the oral sulcular epithelium or the oral epithelium, and desmosomeattachment is four times less common. The sulcus produces a fluid which is composed ofan inflammatory exudate 24 . Mild mechanical agitation of the surface of the sulcularepithelium increases the flow of gingival fluid, and it is believed that no fluid flow occursif the tissue is undisturbed, both in healthy and inflamed states.Studies which have been carried out to examine the penetration of materials into thebody via this route have rarely distinguished between junctional epithelium and oralsulcular epithelium. In addition many animals show differences in the way the epitheliumis attached to the tooth in the sulcular region. Substances which have been claimed atvarious times to penetrate the sulcular epithelium are albumin, endotoxins, thymidine,histamine and horseradish peroxidase, which indicates a permeability of substances up toa molecular weight of 1 million 16 . Particulate material such as polystyrene microsphereswith a 1–3 µm range of diameters have been reported to penetrate the epithelium 25 . It ispossible that substances entering the gingiva do so through the intercellular spaces 26 27 .Topically applied peroxidase was found in the intercellular spaces after 10 minutes andapplication of hyaluronidase, which increases intercellular space, causes increased traceruptake 28 .Gingival disease and ageing are likely to influence drug absorption through thebuccal cavity, since the gum margin may recede or become inflamed. This may allow moreaccess to the underlying connective tissues which have little barrier function to smallmolecules.Improving penetration through the mucosaThere are three methods by which penetration of compounds through the oral mucosa canbe achieved: