Nicotine pectinate salt formulation for colon-targeted delivery: A controlled time-delayed delivery system for nicotine

Deborah Shalev, Department of Pharmaceutical Engineering , Azrieli College of Engineering Jerusalem, Jerusalem, Israel (debbie@jce.ac.il)
Adel Penhasi, Polycaps Ltd. , Jerusalem, Israel
Mila Gomberg, Polycaps Ltd. , Jerusalem, Israel

Nicotine has been shown to have a therapeutic role in treating patients with ulcerative colitis (UC) following epidemiological studies showing that smoking lowers the risk of UC relative to non-smokers [Khasawneh et al., J. Crohn’s and Colitis 2014, 8, 553]. Local delivery of nicotine to the colon is a promising therapy.

Nicotine was combined with a low-methoxylated pectin to form nicotine pectinate (NiP) in a water-isopropanol mixture. The water-isopropyl alcohol ratio was found to be central to the ability to form the NiP. The NiP cores were coated by a combination of Eudragit E (Eud. E) and calcium pectinate (CaP) particulates to give a delayed release corresponding to the desired time of delivery in the colon. The time of onset and rate of release of nicotine from the tablets were controlled by optimizing the core formulation, the ratio between Eud. E and CaP, and the thickness of the film coating. The dissolution profiles of nicotine release from the coated tablets were compared to those of a commercial nicotine resinate (NiR) product, Polacrilex.

Differential scanning calorimetry (DSC) showed that the nicotine significantly changed the thermal properties of the nicotine pectinate complexes relative to the pectin. Furthermore, these properties differed among pectins with different degrees of methoxylation of the carboxylic acid groups (7, 16 and 35% methoxylation).

The binding mode was studied at the molecular level by nuclear magnetic resonance (NMR) and infrared spectroscopy (ATR-FTIR) to determine the precise interactions between the nicotine and pectin that change the polymeric properties of the pectin.

 

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Short Biography of Presenting Author

Deborah did her degrees in Organic Chemistry and Nuclear Magnetic Resonance at Tel Aviv University. She joined the Wolfson Centre of Applied Structural Biology at the Hebrew University of Jerusalem within the framework of a MAGNET consortium for drug design and stayed on as a Senior Research Associate. She is currently Head of the Department of Pharmaceutical Engineering at the Azrieli College of Engineering.