Drug absorption buccal mucosa

One of the most common in vivo methods used to assess the permeability of the buccal mucosa is the buccal absorption test of Beckett and Triggs [13]. In this test, a known volume of a drug solution is introduced into the oral cavity of a subject, who swirls it around for a specified period of time and then expels it. The subject then rinses his or her mouth with an aliquot of distilled water or buffer solution, and the expelled drug solution and rinse are combined and analyzed for drug content. The difference between the initial and final drug concentration in the solution is assumed to be the amount of drug taken up into the oral mucosa. 

The surfaee area available for absorption in the buccal mucosa is much smaller than that in the GI, nasal, reetal, or vaginal mucosae. The bueeal mucosa is continuously bathed by saliva whieh reduees the drug concentration at the absorbing membrane. These two faetors, along with the permeability coefficient of the drug, affeet the overall absorption rate of a drug by this route. In addition, the bueeal mueosa is less permeable than any of the above mentioned mucosae. 

Disk methods for assessing absorption have also been studied where the drug-loaded disk is kept in contact with certain area of the mucosal membrane to allow for absorption. One such polytef disk was used by Anders et al. [35] for the buccal absorption of protirelin. The disk had an area of 10 cm2 and a central circular depression containing the drug. It was removed after 30 min of contact with the buccal mucosa, and blood samples were taken to determine the amount of drug absorbed from the mucosa. 

Solubilization of poorly water-soluble drugs by complexation with cyclodextrins and then delivery via the buccal or sublingual mucosa has been studied as an additional strategy for increasing drug absorption. Cyclodextrins are able to form inclusion complexes with drugs,... 

The buccal permeability of the non-steroidal antiinflammatory drug, diclofenac sodium, has been evaluated in a dog model. The dog was selected because of the similarity of its buccal mucosa to that of man. Analysis of the buccal data indicated that diclofenac sodium permeability followed an essentially zero-order kinetic process with a minimal lag phase. Permeability of the drug was estimated to be 3 mg/cm2.h but significant differences were observed between animals. The absorption rate with the transbuccal delivery device decreased with time whereas the corresponding rate with a saturated solution was constant. This difference was attributed to the time dependency of drug delivery from the device and was modeled on the basis of release from a membrane-dispersed monolith combined with constant buccal permeability. The predictions of the model showed excellent agreement with the experimental data. 

The above procedure was also employed to investigate buccal absorption from the HEMAC experimental delivery device. As in the case of the diffusion cell the drug-loaded disc was positioned on the inner central surface of the buccal mucosa. An impermeable film coated with mucosal adhesive (F-4000, Adhesives Research, Glen Rock, PA) on the periphery was then positioned over the HEMAC disc to prevent dehydration and to secure the device in place on the mucosal surface. The disc was allowed to remain in contact with the mucosa for 4 h before it was removed for quantitation of residual drug content. Blood samples were collected over the same interval as for the saturated solution and processed in the same manner. 

The literature cites numerous studies on buccal absorption in animals and man. However, in most studies experimental conditions were not well defined, making it difficult to draw appropriate conclusions from the experimental data. In the studies reported here the area of buccal mucosa exposed to the drug was carefully controlled, as was the rate of drug delivery in the case of the buccal disc device. The disposition kinetics of the drug was also defined from intravenous data to allow both the rate and extent of absorption to be determined. 

From Figure 1.3 it can be seen that in order to reach the underlying blood capillaries to be absorbed, the drug must pass through at least two epithelial membrane barriers (the apical and basolateral epithelial cell membranes) and also the endothelial membrane of the capillaries. In some cases, for example in stratified epithelia such as that found in the skin and buccal mucosa, the epithelial barrier comprises a number of cell layers rather than a single epithelial cell. Thus the effective barrier to drag absorption is not diffusion across a single membrane as described above, but diffusion across the entire epithelial and endothelial barrier, which may comprise several membranes and cells in series. 

Iontophoresis has the potential to overcome many of the physical barriers to topical drug absorption, and the literature is scattered with reports of the clinical use of iontophoresis for the application of drugs across a variety of epithelia, including the skin, eye, cervix, and buccal mucosa, with mixed success [2]. In general, as detailed below, a successful clinical application... 

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