Intestinal absorption enhancers

Sjosteom, M., Lindfors, L., Ungell, A. L., Inhibition of binding of an enzymatically stable thrombin inhibitor to lumenal proteases as an additional mechanism of intestinal absorption enhancement, Pharm. Res. 1999, 26, 74-79. 

Thanou M, Verhoef JC, and Junginger HE (2001) Chitosan and its derivatives as intestinal absorption enhancers. Adv. Drug Deliv.Rev. 50 S91-S101. 

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. 

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. 

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. 

Contrary to the above-mentioned inhibitors, FK-448 (4-(4-isopropylpiperadinocarbonyl) phenyl 1,2,3,4,-tetrahydro-l-naphthoate methanesulfonate) is a low toxic as well as a potent and specific inhibitor of chymotrypsin. The effectiveness of this substance as an intestinal absorption enhancer has already been demonstrated in rats as well as in dogs. Coadministra-tion of FK-448 led to an enhanced absorption of insulin, which was monitored by a decrease in blood glucose level. The inhibition of chymotrypsin was found to be mainly responsible for the enhanced bioavailability [3]. Camostat mesilate (A,A -dimethyl carbamoylmcthyl-/)-(//-guanidino-benzoyloxy)phenylacetate methanesulfonate) [5] and Na-glycocholate [5,27] are further representatives of this class, exhibiting low toxicity. 

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

Constantinides, P. P, Welzel, G., Ellens, H., Smith, P. L., Sturgis, S., Yiv, S. H., et al. (1996), Water-in-oil microemulsions containing medium-chain fatty acids/salts Formulation and intestinal absorption enhancement evaluation, Pharm. Res., 13(2), 210-215. 

Table 2 Some of the commonly used intestinal absorption enhancers...

Constantinides, P.P. Scalart, J.P. Lancaster, C. Mareello, J. Marks, G. Ellens, H. Smith, P.L. Formulation and intestinal absorption enhancement evaluation of water-in-oil microemulsions incorporating medium-chain glycerides. Pharm. Res. 1994, 77,1385-1390. 

In oral formulations, medium-chain triglycerides are used as the base for the preparation of oral emulsions, microemulsions, self-emulsifying systems, solutions, or suspensions of drugs that are unstable or insoluble in aqueous media, e.g. calciferol. Medium-chain triglycerides have also been investigated as intestinal-absorption enhancers and have additionally been... 

Table 18.8 Compounds Shown to Have Intestinal Absorption-Enhancing Effects ...

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