A novel nicotine pectinate salt formulated in a specific time-controlled delivery system: A new approach for colon-targeted nicotine release

Local delivery of nicotine in the colon can provide effective therapy for patients with ulcerative colitis. A novel tablet formulation containing 5 mg and 10 mg of nicotine was prepared for colon-specific delivery. Nicotine was incorporated into the formulation by preparing nicotine pectinate (NiP) salt from a low methoxy pectin and nicotine in a water-isopropanol mixture. The tablets were coated by a specific combination of Eudragit E (Eud.E), as a film-forming polymer, and calcium pectinate (CaP) particulates to obtain a delayed release corresponding to the time for delivery in the colon. The release profiles of nicotine from coated tablets in phosphate buffer solution, pH 7.5, were characterized by dissolution and compared to those from the formulations based on a commercial nicotine resinate product. The ratio between water and isopropanol was found to be a crucial factor for the interaction between pectin and nicotine and thus the extent of NiP formation. The mode of binding, determined by nuclear magnetic resonance and infrared spectroscopy, was found to be predominantly between the pyrrolidine ring of the nicotine and the carboxyl group of the pectin, with indications of hydrogen bonding to the pyridine ring. Differential scanning calorimetry showed that nicotine binding changed the morphological structure of pectin. By using an appropriate core formulation and adjusting the ratio between Eud.E and CaP in the film coating formulation as well as its thickness, both the rate and time of nicotine release could be controlled to provide precise local delivery in the colon.