Thermally reversible xyloglucan gels as vehicles for rectal drug delivery

The aim of this study was to investigate the potential application of therm oreversible gels formed by a xyloglucan polysaccharide derived from tamarin d seed for rectal drug delivery. Xyloglucan that had been partially degrade d by beta-galactosidase to eliminate 44% of galactose residues formed gels at concentrations of between 1 to 2% w/w at gelation temperatures decreasin g over the range 27 to 22 degrees C with increasing concentration. The in v itro release of indomethacin and diltiazem from the enzyme-degraded xyloglu can gels followed root-time kinetics over a period of 5 h at 37 degrees C; the diffusion coefficients increasing with temperature increase between 10 and 37 degrees C. The ii? vitro release of indomethacin from the gels was s ignificantly more sustained than from commercial suppositories. Measurement of plasma levels of indomethacin after rectal administration to rabbits of the gels and commercial suppositories containing an identical drug concent ration indicated a broader absorption peak following administration of the gels, and a longer residence time. There was no significant difference in b ioavailability of indomethacin when administered by these two vehicles. Mor phological studies of rectal mucosa following a single administration of th e gels showed no evidence of tissue damage. The results of this study sugge st the potential of the enzyme-degraded xyloglucan gels as vehicles for rec tal delivery of drugs. (C) 1998 Elsevier Science B.V. All rights reserved.