AMYLOSE AS A COATING FOR DRUG-DELIVERY TO THE COLON - PREPARATION ANDIN-VITRO EVALUATION USING 5-AMINOSALICYLIC ACID PELLETS

Colon-specific drug delivery may be possible by the application of dri ed amylose films to pharmaceutical formulations. Amylose, one of the m ajor fractions of starch, possesses the ability to form films through gelation, when prepared under appropriate conditions. The microstructu re of the film is potentially resistant to the action of pancreatic cu -amylase but is digested by amylases of the colonic microflora. Howeve r, under simulated gastro-intestinal conditions, coatings made solely of amylose swell, become porous and allow drug release, Incorporation of insoluble polymers into the amylose film, to control amylose swelli ng, provides a solution to this problem. A range of cellulose and acry late based copolymers were assessed, of which a commercially available ethylcellulose (Ethocel(R)) was found to control the swelling most ef fectively. The in vitro dissolution of various coated pellets under si mulated gastric and small intestinal conditions, using commercially av ailable pepsin and pancreatin, was determined and demonstrated the res istance of the amylose-Ethocel(R) coat (1:4 w/w) to such conditions ov er a period of 12 h. With additional thermal treatment of the coat, in vitro drug release under simulated gastric and small intestinal condi tions was prevented further, even after storage of the product for one year. Coated pellets were further evaluated in a batch culture fermen ter, simulating colon conditions, containing an inoculum of mixed faec al bacteria. The in vitro release of 5-aminosalicylic acid from coated pellets in the fermenter system was shown to occur.