Intestine permeation enhancers

Longer chain fatty acids are also effective as intestinal permeation enhancers. Morishita et al. (1998), for instance, could significantly increase the in situ colonic absorption of insulin in rats utilizing emulsions (w/o/w) containing oleic, linoleic or linolenic acid. 

Methyl-p-cyclodextrin/poly(isobutyl-cyanoacrylate) NPs coated with thiolated chitosan Intestinal permeation enhancement of docetaxel [256]... 

Mazzaferro S, Bouchemal K, Skanji R, Gueutin C, Chacun H, Ponchel G. Intestinal permeation enhancement of docetaxel encapsulated into methyl-p-cyclodextrin/ poly(isobutylcyanoacrylate)nanoparticles coated with thiolated chitosan. J Control Release. 2012 162(3) 568-74. 

Aungst B. 2002. Intestinal permeation enhancers. Journal of Pharmaceutical Sciences 429-442. 

At present, despite the advantages offered by the buccal delivery route, such as the bypass of intestinal and hepatic first-pass metabolism for systemic delivery, very few pharmaceutical products employ this route of administration. The reasons that contribute to this situation include (1) high costs associated with development, (2) lack of standardized tests to identify drug candidates suitability for this route, (3) the limited understanding of the impact of metabolism and/or transporters found in the oral cavity mucosa on buccal delivery, and (4) the relatively small number of reports describing the usefulness and safety of excipients/permeation enhancers in humans [82, 83], Therefore, the... 

In recent studies both in vitro (Caco-2 cells) and in vivo in rats, TMC with a degree of trimethylation of 60% was proven to be an excellent intestinal absorption enhancer of the peptide drugs buserelin and octreotide. The observed absolute bioavailability values were 13 and 16% for buserelin and octreotide, respectively [83] (impublished data Fig. 5). Permeation enhancing effects were more responsible for these increased bioavailabilities, rather than the mucoadhesive properties of the TMC polymers. Nevertheless, mucoadhesion is a prerequisite for these polymers in order to further act as absorption enhancers. 

Permeation enhancement by excipients has generated some interest, but there is still much research that needs to be done to elucidate the mechanism of these excipients. PEG-400 (and many other excipients such as polyethylene glycol, poloxamers, polysorbates, and vitamin E) is known to inhibit p-glycoprotein, which may increase the bioavailability of the API, which was a substrate for this efflux pump. On the other hand, it has been demonstrated that PEG-400 can accelerate small intestinal transit, and thereby reduce the bioavailability of some drugs (e.g., ranitidine) (5). 

The enhancement of insulin absorption by sodium caprate (Ci0) in a closed loop model in rats showed the following rank of efficiency colon > ileum > jejunum > duodenum. On the other hand, sodium glycocholate affected the intestinal permeability in a different way. With this surfactant, the order of permeation enhancement was colon > jejunum > duodenum > ileum [95], These results show that the absorption site in the GI tract may strongly affect the effectiveness of permeation enhancer. 

Swenson ES, Milisen WB, Curatolo W (1994) Intestinal permeability enhancement structure-activity and structure-toxicity relationships for nonylphenoxypolyoxyethylene surfactant permeability enhancers. Pharm Res 11 1501-1504 Tomita M, Hayashi M, Horie T, Ishizawa T, Awazu S (1988) Enhancement of colonic drug absorption by the transcellular permeation route. Pharm Res 5 786-789 Tomita M, Sawada T, Ogawa T, Ouchi H, Hayashi M, Awazu S (1992) Differences in the enhancing effects of sodium caprate on colonic and jejunal drug absorption. Pharm Res 9 648-653... 

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