EFFECT OF LUMINAL pH CHANGES ON GUAR GUM-HPMC E15 LV MIXED MATRIX TABLETS FOR MESALAMINE DRUG DELIVERY TO COLON AND STUDY ON IN- VITRO CHARACTERISTICS IN TWO DIFFERENT DISSOLUTION MODELS vs. MARKETED FORMULATION

The study was designed to investigate the impact of colonic pH changes on formulated colon targeted Mesalamine matrix tablets in the treatment of inflammatory bowel disease (IBD). Mesalamine tablets were fabricated with guar gum as Polymer system. The different batches of Mesalamine tablets (GMM1-GMM6) were compressed with increasing proportion of guar gum and HPMC E15 LV. The different buffer conditions were chosen to mimic the pH changes in terminal part of the ileum as well as the colon. A separate two in vitro studies were conducted in all the formulations. The impact of the pH changes on the coated tablets in normal pH condition and reduced pH condition (pH reduced during IBD) were compared. In IBD the pH of the colon falls below its normal level. The extent of pH change depends on the severity of the disease. The study was designed to evaluate the in vitro dissolution characteristics of Mesalamine matrix tablets in a variety of simulated fluids (pH range 1.2, 6, 6.8, 7.2, 5). The results indicated that the impact of pH changes on drug release profile was not affected in the diseased and normal pH condition of the colon. The present treatment methods of IBD mostly depend on pH sensitivity polymers or enteric coating technique. These pH sensitive polymers based colonic devices may not serve the patient needs successfully because the influence of colonic pH on pH sensitive polymer based devices plays an important role in triggering the drug release in target site. The lowered pH condition in diseased state could not trigger the drug release in pH sensitive polymer based devices as it was not the threshold pH of the particular coated polymer. In case of enteric coating there may be a possibility of disintegration of the tablet before reaching the colon due to the contractile movement of GI tract and fluctuation in the GI pH. The present matrix tablets were prepared with guar gum, which cannot be affected by the pH changes of the colon, maintained its integrity better than enteric coated tablets and release the drug in the pre determined pattern and can be used successfully against IBD for better targeting properties. The study results indicate that the formulations of guar gum colon targeted tablets can be used successfully for IBD treatment and better alternate for synthetic polymer based marketed formulations.