The development of colon-targeted dosage forms using natural polymers

Recently, colon-targeted delivery systems have gained importance for the treatment of colon diseases and peroral administration of peptides/proteins. The aim of this study was to develop colon-targeted delivery systems using natural polymers such as sodium alginate and guar gum. Two different types of these polymers with varying viscosities, which have different release mechanisms, were used for this purpose. Mesalamine and ondansetron was chosen as model drugs, which have been used for the treatment of colon diseases, such as inflammatory bowel disease and irritable bowel syndrome. The effect of solubility difference on the release of poorly soluble (mesalamine) and freely soluble (ondansetron) active materials was compared. The physicochemical properties of active materials and polymers were first investigated. Five groups of formulations containing mesalamine/alginate, mesalamine/guar gum, ondansetron/alginate, ondansetron/guar gum and barium suphate for in vivo studies were prepared. The in vitro release studies from the matrix tablets were carried out by flow-through cell apparatus. Four different pH media; pH 1.2, pH 4.5, pH 6.8 and pH 7.4 for 2 hours of each were used for release studies. Galactomannase enzyme was added to pH 7.4 medium for the release studies of tablets containing guar gum. X-ray imaging technique was used to monitor the tablets throughout the gastrointestinal system and to test them in vivo, whether they reached the colon or not in eight healty volunteers. It was found that, mesalamine has pH-dependent solubilitiy and there was no interaction between drugs and polymers as seen with FT-IR. It was observed that, the release of mesalamine decreased by increasing polymer content in the alginate/mesalamine formulations. The viscosity of sodium alginate affected the release and as viscosity increased, the release rate decreased. «ft The results were compared with the commercial tablet Salofalk, which is coated with Eudragit L. The final formulation, which has similar release profiles as the commercial tablet, was used for in vivo studies.154 The viscosity of guar gum has also an effect on the release properties of tablets. It was found that increasing viscosity of guar gum reduced the release rate. The addition of galactomannase enzyme increased the in vitro release rate of the drug from the tablets with guar gum. The initial release ( %8-18) was determined for four hours at pH 1.2 and 4.5 for both drugs with different solubilities. The release was independent of the solubility of the drugs. More polymer was needed for the preparation of colon-targeted formulations of the drug with high solubility. The mesalamine/alginate tablet reached the colon in five of eight healty volunteers in vivo. The tablets disintegrated during the passage through the ileum in the other subjects. It was thought that, the formulations containing alginate may be useful for the treatment of Crohn's disease, which is seen in both terminal ileum and the colon. The mesalamine tablets containing guar gum reached the colon in all of the subjects. It was concluded that, since the release property depends on bacterial degradation in the large intestine, guar gum was a more suitable polymer for colon-targeted studies.