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Hours after meal

Figure 9.13 Hydrogen ion concentrations (CH+) at intervals after a test meal (mean results are shown ± 2SEM); the zero samples were taken just before the meal was begun, and the 1 hour sample just before 45 cm3 of water.

Modified from J. Fordtran, N. Engl. J. Med, 274, 921 (1966).

Hours after meal

Figure 9.13 Hydrogen ion concentrations (CH+) at intervals after a test meal (mean results are shown ± 2SEM); the zero samples were taken just before the meal was begun, and the 1 hour sample just before 45 cm3 of water.

Modified from J. Fordtran, N. Engl. J. Med, 274, 921 (1966).

Table 9.4 Effects of antacids on gastric volume and pH in the ratab

Water Maalox Amphojel

Volume (cm3) 0.29 ± 0.03 1.8 ± 0.3 4.0 ± 0.2 pH 2.2 ± 0.2 7.4 ± 0.1 4.7 ± 0.2

a Reproduced from M. Hava and A. Hurwitz, Eur. J. Pharmacol., 22, 156 (1973).

b Ten rats per group. Measurements on gastric contents made 20 min after the third hourly dose of 1 cm3 water or antacid by gastric intubation.

9.3 Buccal and sublingual absorption

Mouthwashes, toothpastes and other preparations are introduced into the oral cavity for local prophylactic and therapeutic reasons. It is not known to what extent components of these formulations are absorbed and give rise to systemic effects. The absorption of drugs through the oral mucosa, however, provides a route for systemic administration which avoids exposure to the gastrointestinal system. Drugs absorbed in this way bypass the liver and have direct access to the systemic circulation. The sublingual, buccal and gingival tissues are shown diagrammatically in Fig. 9.14. There are many drugs that have not been administered sublingually, although some, like glyceryl trinitrate, have been traditionally administered in this way. The oral mucosa functions primarily as a barrier, however, and it is not a highly permeable tissue, resembling skin more closely than gut in this respect. Table 9.5 lists some commercially available sublingual and buccal delivery systems. Mucosal adhesive systems have been studied for administration of buprenorphine through the gingiva (gums).

9.3.1 Mechanisms of absorption

The oral mucosa comprises

• A mucus layer over the epithelium

• A keratinised layer in certain regions of the oral cavity

• An epithelial layer

• A basement membrane

• Connective tissue

• A submucosal region

While cells of the oral epithelium and epidermis are capable of absorbing material by endocytosis, it does not seem likely that drugs or other solutes would be transported by this mechanism across the entire stratified epithelium. It is also unlikely that active transport processes are operative in the oral mucosa. There is considerable evidence that most substances are absorbed by simple diffusion. The linear relationship between percentage absorption through the buccal epithelium and log P of a homologous series is seen in Fig. 9.15. For example, the buccal absorption of some basic drugs increases (Fig. 9.16), and that of acidic drugs decreases, with increasing pH of their solutions.

Nicotine in a gum vehicle when chewed is absorbed through the buccal mucosa; nicotine levels obtained are lower than those obtained by smoking cigarettes and the high peak levels are not seen. Buccal glyceryl trinitrate has been found to be an effective drug. The buccal route has the advantages of the sublingual route -the buccal mucosa is similar to sublingual

Soft palat Buccal mucosa

Sublingual area

Soft palat Buccal mucosa

Sublingual area

Gingiva Lower lip

Figure 9.14 The anatomy of the oral cavity including the buccal, sublingual and gingival cavities. (From K. Kunth et al., Adv. Drug Del. Rev., 11, 137 (1993).)

Upper lip Gingiva

Hard palate

Hard palate

Buccal mucosa Tongue

Buccal mucosa Tongue

Gingiva Lower lip

Figure 9.14 The anatomy of the oral cavity including the buccal, sublingual and gingival cavities. (From K. Kunth et al., Adv. Drug Del. Rev., 11, 137 (1993).)

Table 9.5 Commercially available drug-delivery systems for systemic delivery by the oral mucosal routea

Mucosal site

Drug

Proprietary name

Dosage form

Sublingual

Glyceryl trinitrate

Nitrostat

Tablets

Lenitral spray

Spray

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