Thermally reversible xyloglucan gels as vehicles for rectal drug delivery.
The aim of this study was to investigate the potential application of thermoreversible gels formed by a xyloglucan polysaccharide derived from tamarind seed for rectal drug delivery. Xyloglucan that had been partially degraded by beta-galactosidase to eliminate 44% of galactose residues formed gels at concentrations of between 1 to 2% w/w at gelation temperatures decreasing over the range 27 to 22 degreesC with increasing concentration. The in vitro release of indomethacin and diltiazem from the enzyme-degraded xyloglucan gels followed root-time kinetics over a period of 5 h at 37 degreesC; the diffusion coefficients increasing with temperature increase between 10 and 37 degreesC. The in vitro release of indomethacin from the gels was significantly 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 concentration indicated a broader absorption peak following administration of the gels, and a longer residence time. There was no significant difference in bioavailability of indomethacin when administered by these two vehicles. Morphological studies of rectal mucosa following a single administration of the gels showed no evidence of tissue damage. The results of this study suggest the potential of the enzyme-degraded xyloglucan gels as vehicles for rectal delivery of drugs.
Miyazaki
S
S
Faculty of Pharmaceutical Sciences, Health Science University of Hokkaido, Ishikari-Tohbetsu, Hokkaido 061-02, Japan.
Suisha
F
F
Kawasaki
N
N
Shirakawa
M
M
Yamatoya
K
K
Attwood
D
D
D000285:Administration, Rectal; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics; D002240:Carbohydrate Sequence; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004110:Diltiazem / Q000008:administration & dosage / Q000493:pharmacokinetics; D004337:Drug Carriers; D005782:Gels / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D005936:Glucans; D006358:Hot Temperature; D007213:Indomethacin / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D008969:Molecular Sequence Data; D011134:Polysaccharides / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D011817:Rabbits; D013488:Suppositories; D014990:Xylans
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002317:Cardiovascular Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005782:Gels; D005936:Glucans; D011134:Polysaccharides; D013488:Suppositories; D014990:Xylans; C029353:xyloglucan; D004110:Diltiazem; D007213:Indomethacin