Most anticancer medications undergo major first-pass metabolism in the intestinal wall, the liver, or both. 5-fluorouracil (5-FU) is known to have erratic oral bioavailability due to first-pass metabolism. The present study aimed to develop 5-FU-loaded microsponges (MS) compressed in enteric-coated tablets as a new colon targeting to colorectal cancer. MS was prepared as a controlled release system for 5-FU and characterized for drug encapsulation efficiency, and surface morphology. Further, hydroxypropyl methylcellulose (HPMC) was mixed with pectin and characterized for their flow as a tablet coat enclosing the core tablets of 5-FU-MS. Moreover, in vitro drug release behavior was studied in different pH media, while the X-ray imaging was used to monitor the in vivo movement of prepared tablets containing 5-FU-MS throughout the GI system. The results showed that MS were spherical in shape and have several pores on their surfaces. The encapsulation efficiency was from 71.80 ± 1.62% - 101.3 ± 2.60%, while the particle size was from 53.11 ± 41.03 - 118.12 ± 48.21 nm. The formulated tablets were fulfilling all official and other specifications and exhibited sustained release of 5-FU only inside the colon. The in vivo human volunteer study of X-ray has shown that the tablets ultimately reached the colon without disturbing in the upper GI system. The obtained carrier formulation is considered as a novel system to deliver 5-FU to the colon tumor with 100% targeting without any drug release in the upper GIT or first-pass metabolism.
Keywords: 5-fluorouracil (5-FU); Colon targeting; HPMC; X-ray imaging; microsponges (MS); pectin.