Site-specific delivery of anti-inflammatory drugs in the gastrointestinal tract: an in-vitro release model.

Mesalazine and budesonide are anti-inflammatory drugs that are used to induce and maintain remission of inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis. Both drug substances are intended to act locally at the inflamed sites of the gastrointestinal tract. The therapeutic objective for per oral treatment with these drugs is to achieve a high concentration of the active drug at the sites of inflammation while minimizing systemic absorption. The aim of this study was to develop a test system able to reflect the changing environment that a dosage form incorporating the anti-inflammatory agent is exposed to as it moves through the gastrointestinal tract. The USP dissolution apparatus 3 was used for all experiments. Compendial, as well as biorelevant, media were used to simulate passage through the gastrointestinal tract under various physiological conditions. Different dosage forms of mesalazine (5-aminosalicylic acid, 5-ASA) and budesonide available on the German market were tested. Although all dosage forms were indicated for the same therapeutic objectives, each of the dosage forms exhibited a characteristic release pattern under in-vitro conditions simulating a passage through the fasted-state gastrointestinal tract. Results from this test series indicate that, in the case of various dosage forms of mesalazine and budesonide used for the therapy of Crohn's disease and ulcerative colitis, release patterns as the dosage form moves through the gastrointestinal tract may vary widely. As the various phenotypes of IBD have different requirements in terms of pattern of distribution of the inflamed sites, and because other aspects of gastrointestinal physiology vary within the patient population, the test methods and approach described here should be very useful in designing therapy tailored to the needs of each individual patient.