NOVEL PHARMACEUTICAL EXCIPIENTS FOR COLON TARGETING

This paper is intended to show which of some newly-synthesized film-fo rming materials can be used with advantage for colon targeting dosage forms or for drug delivery to the human colon. The scientific concept, and the results and experiences obtained with five different types of colon degradable material are discussed. The materials used initially were azo-cross-linked polyisobutylenes of different cross-link densit ies, followed by copolymers made of diisocyanates with sugars or oligo saccharide segments and derivated polysaccharides. The task of the sug ars or oligosaccharides in the copolymers was that of being a desired biodegradation sequence. The urethane should be responsible for the fi lm-forming properties. Locust bean galactomannan and dextran were chos en as raw materials, because their beta-1,4- or alpha-1,6-glycosidic l inks are biodegraded quickly in the human colon. For the use intended, they must however be transformed into derivatives insoluble in water and in gastric and small intestinal fluids. These products are effecti vely completely substituted or wide-meshed cross-linked locust bean ga lactomannans, and dextran esters with varying molecular weight and dif ferent kinds and several degrees of substitution. Some materials are n ot suitable as excipients for colon targeting because they are not bio degradable in the colon, or because of insufficient film-forming prope rties. Some materials show excellent results for colon targeting in vi tro and seem also to be suitable in vivo. In this regard the cross-lin ked locust bean galactomannan and the laurinic acid dextran esters mus t be mentioned particularly.