In-vitro and in-vivo studies of pectin/ethylcellulosefilm-coated pellets of 5-fluorouracil for colonic targeting

Abstract

The aim of the present study was to define in-vitro and in-vivo characteristics of pectin/ethylcellulose-film-coated pellets of 5-fluorouracil (5-FU) for colonic targeting. The pellet cores were coated to different film thicknesses with three different pectin/ethylcellulose formulations using a fluidized bed coater. The gastrointestinal (GI) transit of coated pellets was determined by counting the percentage of coated pellets in the GI lumen by celiotomy at certain times after oral administration. 5FU was administered to rats at a dose of 15 mg kg(-1). The toxicity of 5-FU in the GI tract was evaluated using histological examination. The 1:2 ratio pectin:ethylcellulose-coated pellets with 30% total weight gain (TWG-30%) produced more satisfactory drug-release profiles in the simulated gastric, intestinal and colonic fluids. Most of the coated pellets were eliminated from the stomach in 2 h, moved into the small intestine after 2-4 h, and reached the large intestine after 4 h. After oral administration of coated pellets, 5-FU started appearing in the plasma at 7 h, and reached peak plasma concentration (Cmax) of 3.21+/-2.01 microg mL(-1) at 16 h (Tmax); the Cmax for uncoated pellets was 22.21+/-2.60 microg mL(-1) at Tmax 0.75 h. The TWG-30% formulation showed delayed Tmax, decreased Cmax and prolonged mean residence time compared with uncoated pellets. Marked pathological features in the colon were seen in rats given coated pellets, but no injuries were observed in the upper GI tract. The formulation of TWG-30% could deliver 5-FU to the colon for local action.