Development and In Vitro Characterization of Capecitabine-Loaded Alginate–Pectinate–Chitosan Beads for Colon Targeting

abstract

Colon-targeted capecitabine beads were formulated by an ionotropic gelation method. The sodium alginate to pectin ratio and chitosan concentration were optimized using a 3² full factorial design. Analysis of response surface plots allowed the identification of an optimized formulation with high drug entrapment and controlled release. Insignificant differences in observed and predicted values for responses validated the optimization method. Optimized beads possessed an average diameter of 1395 µm and good flow properties. Their production as spherical beads having a smooth surface was confirmed by scanning electron microscopy. Fourier transform infrared spectroscopy revealed the compatibility of drug with added excipients, while differential scanning calorimetry study confirmed complete drug entrapment in polymer matrix. Higher swelling of beads in phosphate buffer pH 7.4 was obtained in comparison to pH 6.8. An in vitro wash off test indicated 70% mucoadhesion by the beads. In vitro dissolution studies of beads loaded into enteric-coated capsules revealed negligible release in simulated gastric and intestinal fluid, followed by 49.23% release in simulated colonic fluid, in 4 h. The optimized beads were found to be stable for three months at 25 ± 2°C/60 ± 5% RH. In conclusion, the formulated beads showed colon-specific controlled release properties, and thus could prove to be effective for colon cancer treatment.

Keywords:

• capecitabine
• colorectal cancer
• experimental design
• oral delivery

Acknowledgment

The authors acknowledge the Technology Information, Forecasting and Assessment Council (TIFAC), Department of Science & Technology, Government of India, New Delhi for providing research facilities to the team.