Enzymatically activated coated multiparticulates containing theophylline for colon targeting

Abstract

Different types of polymer blends were studied with respect to their potential to provide colon specific drug delivery. The water uptake and dry mass loss kinetics of thin films in media simulating the contents of the upper GIT were used as surrogate parameters for drug permeability of the polymeric networks. Nutriose 100 % fibers, Lycoat NG 73, FOS, wheat dextrin and inulin were studied as “targeting compounds”, which are to be preferentially degraded by bacterial enzymes in the colon of inflammatory bowel disease patients. Ethylcellulose was used as water-insoluble polymer to avoid premature film dissolution/significant swelling in the upper GIT. The “targeting compound”:ethylcellulose blend ratio was varied from 1:2 to 1:5 and the films were exposed to 0.1 M HCl and phosphate buffer pH 6.8, optionally containing pepsin or pancreatin. Furthermore, the mechanical properties of the polymeric networks were measured using a texture analyzer and the puncture test in the dry state as well as upon exposure to media simulating the contents of the upper GIT. Importantly, crack formation in vivo due to the motility of the stomach and small intestine or hydrostatic pressure built up upon water penetration into the delivery systems is unlikely in all cases. Once the polymeric films came into contact with fecal samples from Crohn’s disease and ulcerative colitis patients, the “targeting compound” was (at least partially) degraded by bacterial enzymes, resulting in significant water uptake, dry mass loss and increased permeability for the drug. Theophylline release from pellets coated with 20 % Nutriose 100 % fibers: ethylcellulose 1:5 was effectively limited in media simulating the contents of the upper GIT, but set on as soon as the multiparticulates came into contact with fecal samples.