In situ gelling xyloglucan/pectin formulations for oral sustained drug delivery.
This study has examined the gelation and release characteristics of mixtures of xyloglucan, which has thermally reversible gelation characteristics, and pectin, the gelation of which is ion responsive, with the aim of formulating an in situ gelling vehicle suitable for oral sustained drug delivery. An investigation of the effect of the inclusion of pectin (0.75% (w/w)) on the rheological properties of gels formed from solutions of xyloglucan (1.5 and 2.0% (w/w)) showed a significantly greater gel strength when pectin was present in the formulation. The in vitro release of paracetamol from gels containing 1.5% (w/w) xyloglucan, and 1.5 or 2.0% (w/w) xyloglucan/0.75% (w/w) pectin was diffusion-controlled. Measurement of plasma levels of paracetamol after oral administration to rats of a solution containing 1.5% (w/w) xyloglucan and 0.75% (w/w) pectin showed that a more sustained release and higher drug bioavailability was achieved from the gels formed by the in situ gelation of this formulation compared to that of a 1.5% (w/w) xyloglucan solution; 0.75% (w/w) solutions of pectin did not form gels under these conditions. Visual observation of the contents of the rat stomach at intervals after oral administration showed that the inclusion of pectin in the xyloglucan solutions was effective in reducing gel erosion, so sustaining drug release.
Itoh
Kunihiko
K
Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan. itou@hoku-iryo-u.ac.jp
Yahaba
Masayuki
M
Takahashi
Akie
A
Tsuruya
Reina
R
Miyazaki
Shozo
S
Dairaku
Masatake
M
Togashi
Mitsuo
M
Mikami
Ryozo
R
Attwood
David
D
D000082:Acetaminophen / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D003692:Delayed-Action Preparations; D004058:Diffusion; D005079:Excipients / Q000737:chemistry*; D005782:Gels; D005936:Glucans / Q000737:chemistry*; D008297:Male; D010368:Pectins / Q000737:chemistry*; D019999:Pharmaceutical Solutions; D051381:Rats; D017208:Rats, Wistar; D012212:Rheology; D014990:Xylans / Q000737:chemistry*
D003692:Delayed-Action Preparations; D005079:Excipients; D005782:Gels; D005936:Glucans; D019999:Pharmaceutical Solutions; D014990:Xylans; D000082:Acetaminophen; C029353:xyloglucan; D010368:Pectins