Release of 5-aminosalicylate from an MMX mesalamine tablet during transit through a simulated gastrointestinal tract...

5-Aminosalicylate (5-ASA; mesalamine) is the current first-line treatment for mild to moderate ulcerative colitis, a chronic inflammatory condition that most commonly affects the distal part of the colon. MMXtrade mark mesalamine (Lialdatrade mark [US]; Mezavanttrade mark XL [UK and Ireland]; Mezavanttrade mark [elsewhere]; Shire Pharmaceuticals Inc., Wayne, Pa, under license from Giuliani SpA, Milan, Italy) was created to be a novel, once-daily 5-ASA formulation. MMX mesalamine in tablet form has a pH-dependent, gastroresistant coating and is designed to delay the release of 5-ASA during transit through the upper gastrointestinal tract; it consists of hydrophilic and lipophilic excipients that are designed to prolong the release of 5-ASA throughout the colon. The release kinetics of 5-ASA from an MMX mesalamine tablet were assessed with the use of a dynamic in vitro gastrointestinal tract system (TNO GastroIntestinal Model) that simulates physiologic conditions in the adult human gastrointestinal tract under standardized fed and fasted conditions. This system incorporates removal of released drug via dialysis and automated sampling taken at various sections of the system. Less than 1% of 5-ASA was found to be released from the tablet in the simulated stomach and small intestine (before introduction into the simulated colon). Most of the 5-ASA within each tablet was released in the simulated colon (fasted state conditions: 78.0%; fed state conditions: 68.5%). Substantial quantities were released during the 8- to 18-hour sampling period (49.6 mg/h[fasted] and 40.7 mg/h [fed]). In conclusion, with the use of an in vitro system, the investigators showed that 5-ASA release from an MMX mesalamine tablet was delayed until the tablet reached the simulated colon. Throughout the simulated colon, release of 5-ASA from an MMX mesalamine tablet was prolonged.