Design of sustained-release 5-FU pectinate spheroids using ethyl cellulose and cyclodextrins

Colon-specific drug delivery system is commonly designed through protection of core from upper gastrointestinal fluid via coating typically by means of a mixture of hydrophilic biodegradable polymer such as pectin and hydrophobic polymer such as ethyl cellulose (EC). However, the leaching of pectin from coat composite creates aqueous channels or water-filled pores and leads to fast drug release prior to dosage form reaching the colon region. This study formulates 5-FU into multi-particulate spheroids using pectin as both core and coating substances, combined with EC and cyclodextrins, to prevent early release and enhance drug delivery to the colon for colorectal cancer treatment. A partial replacement of pectin coat in pectin-EC mixture with β-cyclodextrin further reduced the propensity of drug release. However, using acetyl containing cyclodextrin series as coat additive, unexpectedly fast drug release was noted from zinc pectinate spheroids. Hydrophobic part of cyclodextrin exhibited preferential binding to EC. It gave rise to different coat domains from pectin and discontinuity in drug release barrier thereby prompting fast drug release.