Assessment of suitability of guar gum with pH sensitive polymer matrix bases for colon specific delivery

摘要

Degradation of guar gum by colonic microorganisms has been extensively exploited to design colon specific drug delivery systems. Most of these designs suffer from the drawback of very high polymer proportion, need for enteric coating, use of other polysaccharides having better colon specific delivery tendency or compromised therapeutic efficacy due to variation in gastric transit time. In the present investigation, an attempt was made to first understand and rationalize important findings of earlier reports and then identify mechanisms that can be better suited for colonic delivery systems. It was concluded that a pH and transit time dependent mechanism of release preceding colonic microorganism mediated trigger for drug release will provide systems that are having biphasic release profile ideal for colonic delivery. In this study, controlled release colon specific formulations of indomethacin were designed with pH and transit time dependent release profile using combination of responsive polymers Eudragit (L100 or S100) and guar gum in matrix bases. In vitro drug release studies indicated a high burst release from matrix tablets with only guar gum as release retarding polymer, thereby confirming nonsuitability of such matrix for colon specific release. The inclusion of pH responsive polymers Eudragit (L100 and S100) in the matrix base significantly reduced the drug released in the initial phase (0-6 h) followed with controlled release upto 14-16 h. A sigmoidal release pattern was observed from the designed formulations suitable for colonic delivery. This formulation design is expected to show a combined pH and swelling controlled release behavior with potential of a better performance when compared to coated systems and/ only guar gum based matrix tablets.