Thermally reversible xyloglucan gels as vehicles for oral drug delivery.
The potential, as sustained release vehicles, of gels formed in situ following the oral administration of dilute aqueous solutions of a xyloglucan polysaccharide derived from tamarind seed has been assessed by in vitro and in vivo studies. Aqueous solutions of xyloglucan that had been partially degraded by beta-galactosidase to eliminate 44% of galactose residues formed rigid gels at concentrations of 1.0 and 1.5% w/w at 37 degrees C. 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 degrees C at pH 6.8. Plasma concentrations of indomethacin and diltiazem, after oral administration to rats of chilled 1% w/w aqueous solutions of the enzyme-degraded xyloglucan containing dissolved drug, and a suspension of indomethacin of the same concentration were compared. Constant indomethacin plasma concentrations were noted from both formulations after 2 h and were maintained over a period of at least 7 h. Bioavailability of indomethacin from xyloglucan gels formed in situ was increased approximately threefold compared with that from the suspension. The results of this study suggest the potential of the enzyme-degraded xyloglucan gels as vehicles for oral delivery of drugs.
Kawasaki
N
N
Faculty of Pharmaceutical Sciences, Health Science University of Hokkaido, Ishikari-Tohbetsu, Hokkaido 061-02, Japan.
Ohkura
R
R
Miyazaki
S
S
Uno
Y
Y
Sugimoto
S
S
Attwood
D
D
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D002240:Carbohydrate Sequence; D003692:Delayed-Action Preparations; D004110:Diltiazem / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D005782:Gels / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006358:Hot Temperature; D007213:Indomethacin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D008969:Molecular Sequence Data; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D011134:Polysaccharides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D005782:Gels; D014677:Pharmaceutical Vehicles; D011134:Polysaccharides; D004110:Diltiazem; D007213:Indomethacin