Colon delivery

Characteristics of Drugs that Favor Colonic Delivery... 

Recently, Yoshikawa et al. [70] reported a new in vitro dissolution test, called the rotating beads method, for drugs formulated in pressure-controlled colon delivery capsules. This dissolution method was applied to acetominophen sustained-release tablets and two other drugs having low solubility in the colon, tegafur and 5-ASA. There was good correlation between the in vitro dissolution rates and the in vivo absorption rates. 

Vandelli, M.A., Leo, E., Fomi, F., and Bemahei, M.T., In vitro evaluation of a potential colonic delivery system that releases drug after a controllable lag-time, Eur. J. Pharm. Bio-pharm.,Ai-. A%- 5 (1996). 

Yoshikawa, Y., Hu, Z., Kimura, G., Muranishi, M., Yoshikawa, H., and Takada, K., A dissolution test for a pressure-controlled colon delivery capsule rotating beads method, J. Pharm. 

Rubinstein, A., and Gliko-Kabir, I., Synthesis and swelling-dependent enzymatic degradation of borax-modified guar gum for colonic delivery purposes, STP Pharma. Sci., 5 41-46 (1995). 

The use of lectins for colonic delivery is not as well developed as for the small intestine. Nonetheless, the principles are the same in both cases. There are glycoproteins and glycolipids lining the intestine. It is the sugar moieties that are important in lectin-mediated drug delivery. 

This time controlled release tablet with a designated lag time followed by a rapid release may provide an alternative to site-specific delivery of drugs with optimal absorption windows or colonic delivery of drugs that are sensitive to low pH or enzyme action for the treatment of localized conditions such as ulcerative colitis, Crohn s disease, and irritable bowel syndrome (IBS). Also, by controlling a predetermined lag time of drug from dosage form, the release behavior can be matched with the body s circadian rhythm pattern in chronotherapy. 

Obviously, satisfactory colonic absorption of the drug to be delivered is a sine qua non for the successful development of a colonic drug delivery system. However, situations exist when even reduced absorption from the large intestine (compared with the small intestine) would still justify colonic delivery, for instance in the case of a peptide drug that would otherwise be efficiently digested in the small intestine. 

In an effort to develop a peroral application system for insulin, Saffran was the first to use azopolymers as protective colon delivery coating, by use of the aforementioned strategy of azo-linked prodrugs [58, 59], Originally, he used azo-linked copolymers of styrene and hydroxyethylmethacrylate to coat and protect the insulin. However, this approach is not restricted to hydroxyethylmethacrylate and can indeed be accomplished in the same way by an almost unlimited number of similar polymer types. 

With his studies, Saffran heralded two interesting areas of research novel coating systems for colonic delivery coating and novel strategies for the peroral administration of digestible peptide drugs. 

D. Wong, S. Larrabee, K. Clifford, J. Tremblay, and D. Friend, USP apparatus 3 for in vitro screening of colonic delivery formulations, Proceed. Intern. Symp. Control. Rel. Bioact. Mater. 23 555-556 (1996). 

Niwa, K., Takaya, T., Morimoto, T., and Takada, K. (1995), Preparation and evaluation of a time-controlled release capsule made of ethylcellulose for colon delivery of drugs, J. Drug Target., 3, 83-89. 

Takemura, S., Watanabe, S., Katsuma, M., and Fukul, M. (2002), Gastrointestinal transit study of a novel colon delivery system (CODES ) using gamma scintigraphy, Proc. Int. Symp. Controlled Release Bioactive Mater., 27, 445-446. 

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