Background: Mesalazine (5-aminosalicylic acid, 5-ASA) is a drug substance with an antiinflammatory
activity, which is mainly used in the symptomatic treatment of diseases, such as
Ulcerative Colitis, the Crohn's disease and the idiopathic inflammatory bowel disease. Mesalazine
exerts its effect locally in the inflamed area of the intestine and not through systematic absorption,
therefore the investigation of its release characteristics from solid pharmaceutical formulations is of
Objective: The development of novel mesalazine modified release formulations with improved
properties, regarding drug release in the gastrointestinal tract, by utilisation of the Design of
Experiments (DoE) approach.
Methods: D-optimal experimental design was applied. A Simplex Lattice mixture design was used
for the development of suitable capsules containing 4 mini tablets and a D-optimal mixture design
was used for compression-coated tablets, with the following characteristics: ≤10% release in 2 h, to
minimize its degradation in the upper gastrointestinal tract, 20-40% release in 5 h for mesalazine
administration in the small intestine, and quantitative release in 12 h for colonic delivery. The
dissolution experiments were conducted in gastrointestinal-like fluids and pectinases to simulate the
pectinolytic enzymes present in the colon.
Results: The optimal compositions were reached via the desirability function, as a compromise to the
different responses. The optimal solutions for both formulations led to colon-specific delivery of the
active substance with minimal 5-ASA release in the upper gastrointestinal tract and appeared to
conform with the pre-determined characteristics. Hard gelatin capsules, when filled with mini-tablets
led to the aimed modified release profile, having sigmoidal characteristics and compression coated
tablets led to colonic delivery.
Conclusion: Two novel mesalazine formulations were developed with the desirable colonic release,
by conducting a minimal number of experiments, as suggested by DoE experimental design.