Drugs buccal absorption

Wagner, J. G. Sedman, A. J., Quantitation of rate of gastrointestinal and buccal absorption of acidic and basic drugs based on extraction theory, J. Pharmacokinet. Biopharm. 1, 23-50 (1973). 

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. 

Beckett AH, Triggs EJ (1967) Buccal absorption of basic drugs and its application as an in vivo model of passive drug transfer through lipid membranes. J Pharm Pharmacol 19 31S-41S... 

Henry JA, Ohashi K, Wadsworth J, Turner P (1980) Drug recovery following buccal absorption of propranolol. Br J Clin Pharmacol 10 61-65... 

Ho NFH (1993) Biophysical kinetic modeling of buccal absorption. Adv Drug Del Rev 12 61-97... 

McElnay JC (1990) Buccal absorption of drugs. In Swarbrick J, Boylan JC (eds.) Encyclopedia of Pharmaceutical Technology. Marcel Dekker, New York, pp 189-211... 

Rathbone MJ (1991a) Human buccal absorption. I. A method for estimating the transfer kinetics of drugs across the human buccal membrane. Int J Pharm 69 103-108... 

Schumann W, Turner P (1978) Membrane model of the human oral mucosa as derived from buccal absorption performance and physicochemical properties of the beta-blocking drugs atenolol and propranolol. J Pham Pharmacol 30 137-147... 

Other factors which limit mucosal absorption include environmental factors such as the exposure of oral mucosa to salivary flow and the production of shearing forces due to tongue movement and swallowing. Hence in most cases, the actual dose available for buccal absorption is reduced since a high proportion of drug ends up swallowed by the patient. 

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. 

Nicolazzo et al. [52] considered the use of the lipophilic skin penetration enhancers, octisalate and padimate (both used in sunscreens), in comparison to Azone on the buccal absorption of various drugs in vitro. They were found to have limited effect in enhancing the permeation of triamcinolone acetonide (although some increase in tissue uptake was proposed in some cases) relative to Azone, while reducing the penetration of estradiol and caffeine. One interesting report is that of the effect of capsaicin from capsicum, a commonly used food ingredient, which has been reported to enhance the permeability of sulfathiazole in human volunteers [53] presumably by a direct irritation effect on the mucosa. This raised an interesting issue of the effect of diet on oral mucosal permeability. 

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. 

M. Stupfel and M. Mordelet-Dambrlne, Penetration of pollutants In the airways. Bull. Physlopath. resp. 10, 481-509 (1974). A.H. Beckett and R.D. Hossie, Buccal absorption of drugs. Handbook of experimental Pharmacology, 28, 24-26 (1971). 

Membrane storage during buccal absorption of drugs... 

The importance of pH on drug absorption from the mouth has been extensively studied using the buccal absorption model, in which loss of drug from buffered drug solutions placed in the mouth is monitored. The influence of pH on the absorption of the weak base chloroquine and of the weak acid phenobarbitone is shown in Fig. 

However, pH does not always influence the rate or extent of absorption. For example, McElnay et al. found that captopril pharmacodynamic parameters (blood pressure, heart rate, and plasma renin activity) did not differ significantly between buffered and unbuffered sublingual administration, suggesting that manipulation of pH had little effect. It was, therefore, proposed that a mechanism other than passive diffusion was involved in the buccal absorption of this drug. 

Although the undissociated (un-ionized) form of a drug has the higher lipid solubility, the un-ionized moieties themselves have differing lipid solubilities. A common way of assessing the lipid solubility of a drug is to measure its oil-water partition coefficient. As with pH, buccal absorption has been shown to be positively correlated with a drug s oil-water partition coefficient. 

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