ethyl-cellulose and Colitis--Ulcerative

Ulcerative colitis, Crohn's disease and hemorrhage colitis are typical example of colon specific diseases. The targeting of the drugs for these colon specific diseases was attempted by a new technology, where ethylcellulose (EC) was used as pharmaceutical material. Especially, pressure-controlled colon delivery capsule (PCDC) made of EC is a unique system. PCDC was prepared by coating the inner surface of gelatin capsule with water-insoluble polymer, EC. By adjusting the coating thickness of EC membrane to be approximately 40 microns, colon delivery of dug were obtained both in beagle dogs and human volunteers. PCDC containing 5-ASA was prepared and was administered orally to beagle dogs. After administration, 5-ASA appeared into the systemic circulation at 3-5 h which corresponds to the colon arrival time confirmed with sulfasalazine.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Capsules; Cellulose; Colitis, Ulcerative; Colon; Dogs; Drug Delivery Systems; Humans; Mesalamine

Topics: Animals; Colitis, Ulcerative; Colon; Drug Delivery Systems; Drug Implants; Mesalamine; Rats; Solubility

Oral modified-release delivery systems, such as bio-adhesive one, enable drug delivery to affected regions and minimize the side effects by reducing the systemic absorption. Our aim was to develop colon adhesive pellets of 5-aminosalicylic acid (5-ASA) for the treatment of ulcerative colitis. The core of the pellet was formulated from bioadhesive agents, Carbomer 940 and hydroxypropyl cellulose (HPC), by extrusion/spheronization method and coated with Surelease(®) as inner layer for waterproof and with Eudragit(®) S100 as outer layer for pH control. The rat model of ulcerative colitis was used to evaluate the efficiency of our loaded pellets as a drug carrier. Microcrystalline cellulose 101 (PH 301) was found to be the best agent for pellet core. The ratio of CP940 to HPC should be kept as (1:1) to achieve high bioadhesion. When the amount of Surelease(®) was from 16% to 20% and of Eudragit(®) S100 was 28%, the dissolution profiles of coated pellets revealed no drug release in the artificial gastric fluid (pH 1.0) within 2h and less than 10% was released in phosphate buffer (pH 6.0) within 2h whereas complete dissolution was observed in colonic fluid of pH 7.4 for 20 h. The animal experiment showed that 5-ASA loaded colon adhesive pellets had optimal therapeutic effect. We showed a novel approach to prepare effective bioadhesive pellets as colon targeted drug delivery system.

Topics: Acrylic Resins; Adhesiveness; Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Biomarkers; Cellulose; Chemistry, Pharmaceutical; Colitis, Ulcerative; Colon; Disease Models, Animal; Drug Carriers; Excipients; Kinetics; Male; Mesalamine; Polymethacrylic Acids; Rats, Sprague-Dawley; Solubility; Tablets, Enteric-Coated; Technology, Pharmaceutical; Trinitrobenzenesulfonic Acid

The aim of this study was to identify novel polymeric films allowing for the site-specific delivery of drugs to the colon of patients suffering from inflammatory bowel diseases. Ethylcellulose was blended with different types of bacteria-sensitive starch derivatives. The water uptake and dry mass loss kinetics of the systems were monitored upon exposure to media simulating the contents of the stomach, small intestine and colon (including fresh fecal samples from Crohn's Disease and Ulcerative Colitis patients). Importantly, ethylcellulose:Nutriose FB 06 and ethylcellulose:Peas starch N-735 films showed highly promising water uptake and dry mass loss kinetics in all the investigated media, indicating their potential to minimize premature drug release in the upper gastro-intestinal tract, and allowing for controlled release once the colon is reached. This can be attributed to the fact that the starch derivatives serve as substrates for the enzymes, which are secreted by the bacteria present in the colon of inflammatory bowel disease patients. Thus, the identified new polymeric films are adapted to the pathophysiological conditions in the gastro-intestinal tract in the disease state. Furthermore, Nutriose is known to provide pre-biotic effects, which can be of great benefit for these patients.

Topics: Adult; Animals; Bacteria; Cattle; Cellulose; Colitis, Ulcerative; Colon; Crohn Disease; Drug Delivery Systems; Humans; Middle Aged; Rats; Young Adult