Development of a rectal nicotine delivery system for the treatment of ulcerative colitis

The aims of this investigation were: i. to develop a rectal nicotine delive ry system with bioadhesives for the treatment of ulcerative colitis and ii. to evaluate nicotine transport and cytotoxicity of the delivery system usi ng Caco-2 cell culture systems. Rectal nicotine suppository formulations I ere prepared in semi-synthetic glyceride bases (Suppocire AM and AI, Gattef osse Inc.) by fusion method. The in vitro release of nicotine was carried o ut in modified :USP dissolution apparatus i. Differential scanning calorime try:(DSC) and powder X-ray diffraction were used to study the polymorphic c hanges if any in the formulations. An LC method was used for the assay of n icotine. The effect of bioadhesives (glyceryl monooleate (GMO), and Carbopo l) on the nicotine flux was evaluated using Caco-2 cell permeability studie s and Caco-2 cell viability was determined using the MTT toxicity assay. In vitro release studies indicated that the low melting Al base was superior to that of the AM base. Presence of GMO in the formulation enhanced the rel ease of nicotine whereas Carbopol showed an opposite effect. The enhanced r elease of nicotine in the presence of GMO was found to be partly due to the melting point lowering effect of this compound. Caco-2 cell absorption stu dies showed that there was a decrease in the Aux of nicotine in the presenc e of both the bioadhesives, The flux of the fluorescein marker which is use d to study the integrity of the cell monolayers was found to be slightly hi gher only in the presence of 10% (w/w) Carbopol. Nicotine,: Carbopol, and G MO do not have any cytotoxic effect on these cell monolayers within the con centration range used in the formulations. Rectal nicotine formulations con taining bioadhesives were developed and characterized. Both in vitro releas e and cell culture studies have indicated that one can manipulate the nicot ine release from these rectal delivery systems by incorporation of various bioadhesives or the use of different bases in the formulation. Nicotine con centration below 2% (w/v) and bioadhesive concentration below 10% (w/w) do not have any cytotoxic effect on Caco-2 cells. (C) 1999 Published by Elsevi er science B.V. All rights reserved.