Enzymatically degraded Eurylon 6 HP-PG: ethylcellulose film coatings for colon targeting in inflammatory bowel disease patients

J Pharm Pharmacol. 2010 Dec;62(12):1676-84. doi: 10.1111/j.2042-7158.2010.01165.x. Epub 2010 Oct 4.

Abstract

Objectives: 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.

Methods: 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.

Key findings: 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.

Conclusions: 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.

MeSH terms

  • Amylose*
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Bacteria / metabolism
  • Cellulose / analogs & derivatives*
  • Colon / drug effects*
  • Colon / metabolism
  • Colon / microbiology
  • Delayed-Action Preparations
  • Drug Delivery Systems
  • Drug Stability
  • Enzymes / metabolism
  • Excipients
  • Gastrointestinal Tract / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Inflammatory Bowel Diseases / drug therapy*
  • Inflammatory Bowel Diseases / metabolism
  • Mesalamine / administration & dosage
  • Mesalamine / chemistry
  • Mesalamine / therapeutic use*
  • Polymers
  • Starch*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Delayed-Action Preparations
  • Enzymes
  • Excipients
  • Polymers
  • Mesalamine
  • ethyl cellulose
  • Cellulose
  • Starch
  • Amylose