Application of Eudragit P-4135F for the delivery of ellagic acid to the rat lower small intestine

Based on the assumption that the delivery of ellagic acid to its site of ac tion would show an antiinflammatory activity in inflammatory bowel disease (IBD), we have prepared microspheres using a new pH-sensitive polymer, Eudr agit P-4135F (P-4135F), to deliver ellagic acid to the lower small intestin e in rats. The microspheres were spherical in shape and the mean diameters were approximately 100-150 mum. The amount of ellagic acid released from th e microspheres decreased by increasing the formulated amount of P-4135F. Th e release characteristics of ellagic acid were pH-dependent. By considering the factors loading efficiency and microsphere particle size distribution, ellagic acid-2 microspheres (P-4135F/ellagic acid = 1.65) were selected fo r further investigation. in a dissolution study, more than 95 % ellagic aci d was released within 0.5 h in pH 7.4 and 8.0 buffers. The release percent of ellagic acid was less than 40% in pH 6.8 and 7.0 and was less than 10% i n pH 5.6 and 5.9. To observe the dissolution sites of the microspheres in t he rat small intestine fluorescein was formulated in the microspheres as a tracer drug along with ellagic acid (50 mg kg(-1)). After intraduodenal adm inistration of fluorescein-labelled microspheres to rats, the plasma fluore scein level started to increase at 0.5 h, by which time the microspheres ha d reached the middle part of the ileum. Microspheres started to dissolve wi thin 1.0 h and the peak plasma fluorescein concentration was observed at 3. 0 h, when the majority of the administered microspheres were dissolved in t he terminal ileum. These results suggested that P-4135F microspheres could deliver ellagic acid to the lower part of the small intestine, and that the released ellagic acid would be distributed into the caecum and the ascendi ng colon.