Matrices for site-specific controlled-delivery of 5-fluorouracil to descending colon

• Published in: Journal of controlled release 2005-02, Vol.102 (3), p.669-677
• Main Authors: Zambito, Y., Baggiani, A., Carelli, V., Serafini, M.F., Di Colo, G.
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Animals; Biological and medical sciences; Chitosan hydrochloride; Colon, Descending - drug effects; Colon, Descending - metabolism; Colon-specific delivery; Controlled-release matrices; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - pharmacokinetics; Drug Delivery Systems - methods; Fluorouracil - administration & dosage; Fluorouracil - pharmacokinetics; General pharmacology; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Rats; Rats, Wistar; Release mechanism
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2004.11.001

Colon-specific controlled-delivery 5-fluorouracil (5-FU) matrices for the treatment of colorectal carcinoma were prepared and evaluated. Matrices are destined to be introduced into enteric-coated capsules and thereby carried to and liberated in the ileum. There, drug release should be prevented until matrices reach descending colon where release should occur. Matrices (50 mg, diameter 0.6 mm) were prepared by compression of powders or of granules prepared by melt granulation. The ingredients comprised 30–70% w/w 5-FU, glyceryl palmitostearate as rate-controlling material and 5% w/w Aerosil as glidant. Drug release was measured by the rotating basket method. The matrix containing 60% w/w drug, prepared by compression of powders, was appropriate to make the planned system, in virtue of its fairly high drug load and its nearly constant and reasonable release rate. This matrix was spray-coated with Eudragit S100 (EUD). Subsequently, an external layer of chitosan hydrochloride (CH–HCl) was applied by a dipping-drying technique. When transit of coated matrix through ileum (phosphate buffer (PB) pH 7.4), ascending colon (PB pH 6 containing rat cecal contents) and descending colon (PB pH 7.4) was simulated in vitro, the pH 4.7 of the CH–HCl gel layer and the pH 6 of the ascending colon prevented dissolution of the protective EUD film until descending colon was reached, then controlled release started. The present small matrices can enter size no. 00 capsules. Considering that each capsule contains 10 matrices, the maximal dose is 300 mg.