Percutaneous absorption of non-steroidal anti-inflammatory drugs from in situ gelling xyloglucan formulations in rats.
The potential of gels formed in situ by dilute aqueous solutions of a xyloglucan polysaccharide derived from tamarind seed as sustained release vehicles for percutaneous administration of non-steroidal anti-inflammatory drugs has been assessed by in vitro and in vivo studies. Chilled aqueous solutions of xyloglucan that had been partially degraded by beta-galactosidase formed gels at concentrations of 1-2% w/w when warmed to 37 degrees C. The in vitro release of ibuprofen and ketoprofen at pH 7.4 from the enzyme degraded xyloglucan gels and the subsequent permeation of these fully ionized drugs through cellulose membranes followed root-time kinetics over a period of 12 h after an initial lag period. Diffusion coefficients were appreciably higher when the drugs were released from 1.5% w/w xyloglucan gels than when released from 25% w/w Pluronic F127 gels formed in situ under identical conditions. The difference in release rates was attributed to differences in the structure of the gels. The permeation rate of ibuprofen through excised skin was higher than that of ketoprofen when released from both gels, but of similar magnitude through cellulose membranes. Plasma concentrations of ibuprofen and ketoprofen from gels formed in situ following topical application of chilled aqueous solutions of xyloglucan and Pluronic F127 to the abdominal skin of rats were compared. The bioavailabilities of ibuprofen and ketoprofen were significantly higher when released from xyloglucan gels compared to Pluronic F127 gels. Occlusive dressing techniques had a greater enhancing effect on the bioavailability of ibuprofen when released from Pluronic gels.
Takahashi
A
A
Faculty of Pharmaceutical Sciences, Health Science University of Hokkaido, Ishikari-Tohbetsu, Japan.
Suzuki
S
S
Kawasaki
N
N
Kubo
W
W
Miyazaki
S
S
Loebenberg
R
R
Bachynsky
J
J
Attwood
D
D
D000279:Administration, Cutaneous; D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002482:Cellulose / Q000737:chemistry; D004337:Drug Carriers; D005782:Gels; D005936:Glucans; D007052:Ibuprofen / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007660:Ketoprofen / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D008566:Membranes; D020442:Poloxamer / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption; D014990:Xylans
D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D005782:Gels; D005936:Glucans; D011134:Polysaccharides; D014990:Xylans; D020442:Poloxamer; C029353:xyloglucan; D002482:Cellulose; D007660:Ketoprofen; D007052:Ibuprofen