Alaa A. Abdul Rasool

Studying the Release Profile of 5-Fluorouracil Prepared By Controlled Porosity Osmotic System As A Colon Targeting

In this study, different formulas (F1-F7) containing 4 mg of 5-fluorouracil (5-FU) were prepared as a tablet in form of CPOP-CT. The core of these formulas contained citric acid, sodium chloride, LMCh, MMCh, ProSolv SMCC®90 and magnesium stearate mixed with 5-FU. The formulas were double coated by an inner layer containing chitosan and PEG-400 and outer layer as an enteric coating containing Eudragit®L100-55, triethyl citrate and talc. The solubility of 5-FU in different dissolution media (pH 5, pH 7) was studied. The results indicated increase of LMCh and decrease of citric acid lead to slow the release of 5-FU for F1, F2, F3, F4, F5, F6 and F7 in simulated colonic fluid with 61%, 29%, 32%, 43%, 52%, 39% and 68%, respectively within 21 h. In addition, the release rate of 5-FU was affected by changing the weight gain percentages of semipermeable CAM. 6% and 10% weight gains of F3 released 5-FU completely within times (t100% ) of 46 h and 65 h, respectively which are acceptable with colonic transit time (78 h) compared with 14% weight gain (t100% = 135 h).  In SCF, the enzymatic effect on the release of 5-FU within 21 h for F6 was studied which synthetic almond emulsin β-glucosidase and human fecal enzyme increased release of 5-FU with 26% and 39%, respectively compared to 18% release with no enzyme. Degradation effect of these enzymes made pores in semipermeable to release drugs and then modulate the drug kinetic from zero order into first order.