Absorption enhancers fatty acids

The enhancement of UV absorption of fatty acids by benzylation is another approach to the HPLC analysis of trace amounts of fatty acids [41]. The reagents l-benzyl-3-p-tolyl-triazene or l-p-nitrobenzyl-3 p-tolyltriazene are used. The reaction proceeds according to the equation shown in Fig.4.17. 

Permeation enhancers are used to improve absorption through the gastric mucosa. Eor example, oral dehvery of insulin (mol wt = 6000) has been reported from a water-in-oH- emulsion containing lecithin, nonesterified fatty acids, cholesterol [57-88-5], and the protease inhibitor aprotinin [9087-70-1] (23). 

Kimura, Y. Hosoda, Y. Shima, M. Adachi, S. Matsuno, R., Physicochemical properties of fatty acids for assessing the threshold concentration to enhance the absorption of a hydrophilic substance, Biosci. Biotechnol. Biochem. 62, 443 447 (1998). 

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-... 

Ganem-Quintanar A, Quintanar-Guerrero D, Falson-Rieg F, Buri P (1998) Ex vivo oral mucosal permeation of lidocaine hydrochloride with sucrose fatty acid esters as absorption enhancers. Int J Pharm 173 203-210... 

Cano-Cebrian MJ, Zornoza T, Granero L, and Polache A (2005) Intestinal absorption enhancement via the paracellular route by fatty acids, chitosans and others A target for drug delivery. Curr. Drug Deliv. 2 9-22. 

Lindmark T, Kimura Y, Artursson P (1998) Absorption enhancement through intracellular regulation of tight junction permeability by medium chain fatty acids in Caco-2 cells. J Pharmacol Exp Ther 284 362-369... 

The addition of absorption enhancers, like bile salts (glycocholate), fatty acids (Unoleic acid), surfactants (lecithins, polyoxyethylene-9-lauryl ether or N-lauryl-P-D-maltopyra-noside) and chelators (EDTA) can significantly increase the absorption of various proteins. However, the application of enhancers is limited by their toxicity. For example polyoxyethyl-ene-9-lauryl ether and sodium glycocholate caused serious oedema, haemorrhage and inflammation of the lung after intratracheal instillation [39]. 

Both interferon-a and - 3 have been shown to be absorbed across the rectal mucosa when given with the fatty acid linolenic acid as mixed micelles. In the absence of a permeation enhancer, rectally administered interferons (165 aa) do not achieve detectable levels in blood nor lymph. With 0.56% linolenic acid, a significant degree of lymphatic absorption of interferon-a and -P was detected [20]. The rectally absorbed interferon first distributes into the lymphatics, and interferon concentration is much higher in lymph than... 

Dimethylhydrazine is well absorbed from the colon of the rat, as shown by an in-vivo perfusion technique (Meshkinpour et al., 1985). The absorption was enhanced significantly by bile acids and by hydroxy-fatty acids fatty acids had no significant effect. 

Constantinides, P.P., et al., Water-in-oil microemulsions containing medium-chain fatty acids/salts formulation and intestinal absorption enhancement evaludfibarm. Res., 13, 210, 1996. 

Mori, S., et al. 2004. Studies on the intestinal absorption of low molecular weight heparin using saturated fatty acids and their derivatives as an absorption enhancer in rats. Biol Pharm Bull 27 418. 

In the past two decades, many studies have tested adjuvants that act by either permeabilizing the rectal mucosa or inhibiting drug degradation. Oral and rectal routes of drug administration are unsuitable for adequate absorption of various compounds with a peptide or protein structure and of several hydrophilic antibiotics. The use of absorption enhancers, e.g., salicylates, enamines, surfactants, and straight-chain fatty acids, has gained wide interest... 

An important issue that has been recognized recently concerns the potential adverse effect of absorption enhancers on the rectal mucosa, as shown in rats after a single application [61,62], Safety evaluation of the applicability of absorption enhancers is imperative. In clinical application, medium-chain fatty acids such as sodium caprate are used only for suppositories containing antibiotics [36],... 

Lindmark, T., T. Nikkila, and P. Artursson. 1995. Mechanisms of absorption enhancement by medium chain fatty acids in intestinal epithelial Caco-2 cell monolayers. J Pharmacol Exp Ther 275 958. 

Van Hoogdalem, E.J., et al. 1988. Absorption enhancement of rectally infused cefoxitin sodium by medium-chain fatty acids in conscious rats Concentration-effect relationship. Pharm Res 5 453. 

Other fatty acids as absorption enhancers have been reported. Ogiso et al. [112] demonstrated that lauric acid (C12) produced the largest increase in permeation rate, penetration coefficient, and partition coefficient of propranolol. Onuki et al. [113] reported that docosa-hexaenoic acid (DHA) has a strong insulin permeability enhancement effect and little toxicity, compared to oleic acid and eicosapentaenoic acid (EPA) using a water-in-oil-in-water (W/O/W) multiple emulsion with no or little mucosal damage. 

Murakami, M., et al. 1988. Intestinal absorption enhanced by unsaturated fatty acids. Inhibitory effect of sulfhydryl modifiers. Biochim Biophys Acta 939 238. 

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. 

Fujita, T., Fujita, T., Morikawa, K., et al. Improvement of intestinal absorption of human calcitonin by chemical modification with fatty acids Synergistic effects of acylation and absorption enhancers. Int. J. Pharm. 134 47—57, 1996. 

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