Acids 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). 

Ho, N. F., Higuchi, W. I., Quantitative interpretation of in vivo buccal absorption of n-alkanoic acids by the physical model approach, /. Pharm. Sci. 1971, 60, 537-541. 

Beckett AH, Moffat AC (1969) Correlation of partition coefficients in n-heptane-aqueous systems with buccal absorption data for a series of amines and acids. J Pharm Pharmacol 21 144S-150S... 

Rathbone MJ (1991b) Human buccal absorption. II. A comparative study of the buccal absorption of some parahydroxybenzoic acid derivatives using the buccal absorption test and a buccal perfusion cell. Int J Pharm 74 189-194... 

Figure 2. Buccal absorption at six pH s of an amine and an acid. Equation 6.

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. 

Buccal Absorption of Acids. When a data set contains high log D values, quadratic terms in log D enter in to regression analyses just as with high log P s. Beckett and Moffat (6) measured the buccal absorption rates for a range of carboxylic acids (Table III). Again we find the rates are correlated well with an equation in log D terms alone (eq 7). An optimum log D of 3.28 can be calculated. The best alternative analysis is eq 8 7). 

Buccal Absorption of Organic Acids and Physicochemical Constants... 

Buccal Absorption at Various pH s. I would like to show you one additional example that supports the premise that log D correlations relate to the amount of a compound at a site, that I find very impressive. Not only can one combine data for the absorption of acids and bases, but the regression results hold for any pH (any pH not affecting the system itself). Schurman and Turner (8) measured the buccal absorption rate of propranolol and n-hexylphenylacetic acid from pH 4 to pH 9. (Table IV). The absorption rate for these compounds is well described by the simple equation 9. A quadratic equation (10) provides an even better fit. 

Buccal Absorption of an Acid and a Base at Six pH Values and Physicochemical Constants Used for Eq 9, 10... 

Eq. Ill [345] correlates the buccal absorption rate constants of an acid (p-hexylphenylacetic acid, pK = 4.36) and a base (propranolol, pK = 9.45) at different pH values with log Papp values (Table 16) [345, 470]. 

Table 16. Buccal absorption of propranolol and p-hexylphenylacetic acid at dilTerenl pH values [345,470]...

Much more complex models correlate the buccal absorption rate constants of these acids at different pH values, e.g. eq. 165 [479]. Even the rate constants for acidic and basic drugs can be combined to obtain one equation by using log Papp instead of log P (eq. Ill, chapter 4.5). 

The penetration of some steroids through skin samples vitro is influenced by the solvent composition consisting of volatile and nonvolatile oils . As the proportion of volatile oil is increased skin penetration increases, presumably due to the Increased thermodynamic activity of drug after solvent evaporation. The efficiency of buccal absorption of a series of amines and carboxylic acidsand of imipramine and its metabolites correlated well with their partition coefficients. Substituent effects among phenylacetic acids on buccal absorption were also reported" . 

Drug transport and availability have also been measured for routes of administration other than oral. Rectal absorption of acetaminophen and salicylate , buccal absorption of barbituates and a series of n-alka-noic acids , peritoneal dialysis " , penetration across the vitreous barrier of the eye , and the significance of vehicle composition in the skin penetration of fluocinolone acetonide were all studied. 

Penetration enhancers are low molecular weight compounds that can increase the absorption of poorly absorbed hydrophilic drugs such as peptides and proteins from the nasal, buccal, oral, rectal, and vaginal routes of administration [186], Chelators, bile salts, surfactants, and fatty acids are some examples of penetration enhancers that have been widely tested [186], The precise mechanisms by which these enhancers increase drug penetration are largely unknown. Bile salts, for instance, have been shown to increase the transport of lipophilic cholesterol [187] as well as the pore size of the epithelium [188], indicating enhancement in both transcellular and paracellular transport. Bile salts are known to break down mucus [189], form micelles [190], extract membrane proteins [191], and chelate ions [192], While breakdown of mucus, formation of micelles, and lipid extraction may have contributed predominantly to the bile salt-induced enhancement of transcellular transport, chelation of ions possibly accounts for their effect on the paracellular pathway. In addition to their lack of specificity in enhancing mem-... 

Evered DF, Sadoogh-Abasian F, Patel PD (1980) Absorption of nicotinic acid and nicotinamide across human buccal mucosa in vivo. Life Sci 27 1649-1651... 

Similarly, the 4-methoxy-2-naphthylamides of Leu, Ala, Arg, and Glu (6.1, R=side chain of amino acid, R =MeO) were used to assess the type and activity of aminopeptidase in homogenates of conjunctival, nasal, buccal, duodenal, ileal, rectal, and vaginal tissues from rabbits. This systematic comparison afforded a better understanding of the role of the aminopeptidase barrier in peptide absorption from oral vs. non-oral routes [18]. In a comparable manner, the y-glutamyltranspeptidase and dipeptidase activities were investigated in mammary tissue with the 4-nitroanilides of Leu, Met, Lys, Glu, and Asp (6.2, R=side chain of amino acid) [19]. 

Fatty acid esters would be predicted to have little irritation or toxic effects. Ex vivo permeability studies conducted in porcine buccal mucosa showed significant permeation enhancement of an enkephalin from liquid crystalline phases of glycerine monooleate [32]. These were reported to enhance peptide absorption by a cotransport mechanism. Diethylene glycol monoethyl ether was reported to enhance the permeation of essential oil components of Salvia desoleana through porcine buccal mucosa from a topical microemulsion gel formulation [33]. Some sucrose fatty acid esters, namely, sucrose laurate, sucrose oleate, sucrose palmitate, and sucrose stearate, were investigated on the permeation of lidocaine hydrochloride [34], with 1.5% w/v sucrose laurate showing a 22-fold increase in the enhancement ratio. 

Azone (laurocapram) is used extensively as a transdermal permeation enhancer, and has also found use in buccal drug delivery. It is a lipophilic surfactant in nature (Figure 10.4). Permeation of salicylic acid was enhanced by the pre-application of an Azone emulsion in vivo in a keratinized hamster cheek pouch model [35]. Octreotide and some hydrophobic compounds absorption have also been improved by the use of Azone [36], Azone was shown to interact with the lipid domains and alter the molecular moment on the surface of the bilayers [37], In skin it has been proposed that Azone was able to form ion pairs with anionic drugs to promote their permeation [38],... 

The small intestine contains a wide variety of transporters (amino acid transporters, oligopeptide transporters, glucose transporters, lactic acid transporters etc.) on the apical membrane of the epithelial cells, which serve as carriers to facilitate nutrient absorption by the intestine. On the basolateral membrane, the presence of amino acid and oligopeptide transporters has been demonstrated. Active transport mechanisms for di- and tri-peptides have also been demonstrated in the nasal and buccal epithelia. 

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