Potential of calcium pectinate beads for target specific drug release to colon

Abstract

A pectin-based colon specific delivery system bearing 5-fluorouracil (5-FU) was developed for effective delivery of drug to the colon. Calcium pectinate gel (CPG) beads were prepared by ionotropic gelation method followed by enteric coating with Eudragit S-100. The CPG beads formed were spherical with smooth surfaces. CPG beads size was found to be in the range of 1.32 ± 0.12–1.88 ± 0.08 mm. The in vitro drug release was investigated using USP dissolution rate test paddle type apparatus in different simulated mediums. Release in PBS (pH 7.4) and simulated gastric fluid showed almost similar pattern and rate, whereas a significant increase in percent cumulative drug release (58.3 ± 1.36%) was observed in medium containing rat caecal content, i.e. the amount of the drug released from the formulation was found to be 49.2 ± 2.29 and 58.3 ± 1.36% of drug with 2 and 4% w/v caecal matter after 24 h whereas in control study 33.2 ± 1.19% of drug was released. Moreover, to induce the enzymes that specifically act on pectin, the rats were treated with 1 ml of 1% w/v dispersion of pectin for 2 and 4 days and release rate studies were repeated in SCF in the presence of 2 and 4% w/v of caecal matter. A marked improvement in the drug release was observed in presence of caecal matter obtained after induction when compared to those without induction. The percentage of drug released after 24 h release was observed to be 69.3 ± 2.81 and 86.7 ± 3.15%, respectively, with 2 and 4% w/v rat caecal matter obtained after 2 days of enzyme induction, and 82.4 ± 3.15 and 98.7 ± 4.26%, respectively, after 4 days of enzyme induction. In vivo data showed that Eudragit S-100 coated calcium pectinate beads delivered most of its drug load (93.2 ± 3.67%) to the colon after 9 h, which reflects its targeting potential to the colon. It is concluded that orally-ssadministered 5-FU loaded Eudragit S-100 coated calcium pectinate beads can be used effectively for the specific delivery of drug to the colon.

Keywords: :

• Colon targeted drug delivery
• biodegradable polymer
• calcium pectinate beads
• colorectal cancer
• Eudragit S-100, 5-FU