ethyl-cellulose and Inflammatory-Bowel-Diseases

Film coatings based on blends of Eurylon 6 HP-PG (a hydroxypropylated and pregelatinized high amylose starch) and ethylcellulose were to be evaluated as promising coating materials for site-specific drug delivery to the colon of patients suffering from inflammatory bowel diseases.. Pellet starter cores containing 60% 5-aminosalicylic acid were prepared by extrusion/spheronization and coated with different Eurylon 6 HP-PG:ethylcellulose blends at various coating levels. Drug release was measured in media simulating the contents of the upper gastrointestinal tract (in the presence and absence of enzymes) as well as in media simulating the contents of the colon.. 5-Aminosalicylic acid release could effectively be suppressed in 0.1 N HCl and phosphate buffer pH 6.8, optionally containing pepsin or pancreatin, but occurred as soon as the pellets came into contact with culture medium inoculated with faecal samples from inflammatory bowel disease patients. This can be attributed to the partial degradation of the starch derivative by enzymes secreted by bacteria present in the colon of these patients.. The presented drug delivery system is adapted to the pathophysiological conditions in inflammatory bowel disease patients. Furthermore, drug release remained unaltered upon 1 year open storage.

Topics: Amylose; Anti-Inflammatory Agents, Non-Steroidal; Bacteria; Cellulose; Colon; Delayed-Action Preparations; Drug Delivery Systems; Drug Stability; Enzymes; Excipients; Gastrointestinal Tract; Humans; Hydrogen-Ion Concentration; Inflammatory Bowel Diseases; Mesalamine; Polymers; Starch

The major aim of this work was to optimize the properties of novel polymeric films based on blends of ethylcellulose and Nutriose (a water-soluble, branched dextrin). Such blends were recently shown to be highly promising for the site-specific delivery of drugs to the colon in patients suffering from inflammatory bowel diseases, in particular Crohn's disease and ulcerative colitis. Importantly, and in contrast to various other colon targeting approaches, the system is adapted to the pathophysiological conditions in the disease state. However, it is yet unknown how desired membrane properties, especially water uptake and dry mass loss kinetics as well as mechanical stability can be adjusted to the specific needs of particular drug treatments. Different highly efficient and easy to apply tools were identified altering the membrane's properties, in particular their mechanical resistance required to withstand the shear forces resulting from the motility of the upper GIT and the hydrostatic pressure built up within the devices upon contact with aqueous media. This includes the variation of the Nutriose:ethylcellulose blend ratio and initial plasticizer content. Importantly, Nutriose also exhibits significant pre-biotic activity, normalizing the microflora in the patients' colon, which is of major clinical benefit in the case of inflammatory bowel diseases.

Topics: Cellulose; Colon; Delayed-Action Preparations; Dextrins; Drug Carriers; Humans; Inflammatory Bowel Diseases; Membranes, Artificial; Permeability; Plasticizers; Stress, Mechanical; Tablets, Enteric-Coated; Water

The aim of this study was to prepare and characterize novel types of polymer coated pellets allowing for the site-specific delivery of drugs to the colon. 5-Aminosalicylic acid (5-ASA)-loaded beads were prepared by extrusion-spheronization and coated with different Nutriose:ethylcellulose blends. In vitro drug release from these systems was measured under various conditions, including the exposure to fresh fecal samples from inflammatory bowel disease patients under anaerobic conditions. Nutriose is a starch derivative, which is preferentially degraded by enzymes secreted by the microflora in the colon of Crohn's disease and ulcerative colitis patients. Interestingly, the release of 5-ASA (which is commonly used for the local treatment of inflammatory bowel diseases) could effectively be suppressed upon exposure to release media simulating the conditions in the upper GIT, irrespective of the degree of agitation and presence or absence of enzymes. But as soon as the pellets came into contact with fecal samples of inflammatory bowel disease patients, the release rate significantly increased and the drug was released in a time-controlled manner. Thus, this novel type of colon targeting system is adapted to the pathophysiology of the patient. Furthermore, culture media containing specific colonic bacteria are presented providing an interesting potential as substitutes for fresh fecal samples.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Capsules; Cellulose; Colon; Delayed-Action Preparations; Drug Delivery Systems; Excipients; Feces; Gastrointestinal Tract; Humans; Inflammatory Bowel Diseases; Mesalamine; Polymers; Tablets, Enteric-Coated

The site-specific delivery of drugs to the colon can be highly advantageous for various applications, including the local treatment of inflammatory bowel diseases. The aim of this study was to provide efficient tools that can be used to easily adjust the key properties of novel polymeric film coatings allowing for colon targeting.. Free films based on blends of ethylcellulose and different types of starch derivatives (partially being pregelatinized, acetylated, and/or hydroxypropylated) were prepared and characterized.. The key properties of the polymeric systems can effectively be adjusted by varying the polymer blend ratio and type of starch derivative. This includes the water uptake and dry mass loss kinetics as well as the mechanical properties of the films before and upon exposure to aqueous media simulating the contents of the upper GIT.. Broad ranges of film coating properties can easily be provided, being adapted to the needs of the respective drug treatment.

Topics: Cellulose; Chemistry, Pharmaceutical; Colon; Delayed-Action Preparations; Drug Carriers; Drug Delivery Systems; Excipients; Humans; Inflammatory Bowel Diseases; Starch; Water