In situ gelling xyloglucan/alginate liquid formulation for oral sustained drug delivery to dysphagic patients.
BACKGROUND
The oral administration of liquid dosage forms of suitable consistency and with sustained release characteristics may provide a means of improving the compliance of geriatric patients who experience difficulties in swallowing conventional solid dosage forms.


OBJECTIVE
We have designed and evaluated liquid preparations for administration to dysphagic patients, composed of aqueous mixtures of xyloglucan, which has thermally reversible gelation characteristics, and sodium alginate, which has ion-responsive gelation characteristics.


METHODS
The gelation and in vitro and in vivo release characteristics of liquid formulations containing appropriate concentrations of xyloglucan and sodium alginate with mannuronate/guluronate ratios of either 0.5 or 0.8 were assessed.


RESULTS
Aqueous mixtures of 1.5% xyloglucan and 0.5% alginate had suitable viscosities for ease of swallowing and appropriate gelation temperatures (approximately 33 degrees C) to ensure in situ gelation following oral administration. The in vitro release of paracetamol at pH 5.0 from gels formed by these formulations and also by a 1.5% xyloglucan solution was diffusion-controlled. Plasma levels of paracetamol after oral administration to gastric-acidity controlled rats (pH 5) of a solution containing 1.5% xyloglucan/0.5% alginate showed that a more sustained release was achieved from the gels formed by the in situ gelation of this formulation compared with that of a 1.5% xyloglucan solution. Visual observation of the contents of the rat stomach after oral administration showed that the inclusion of alginate in the xyloglucan solutions was effective in reducing gel erosion, so sustaining drug release.


CONCLUSIONS
Liquid formulations of xyloglucan and sodium alginate in appropriate proportions are of suitable consistency for ease of administration to dysphagic patients and form gels in situ in the rat stomach capable of sustaining the release of paracetamol over a 6-hour period.
Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan. itou@hoku-iryo-u.ac.jp
Kunihiko
K
Itoh
Reina
R
Tsuruya
Tetsuya
T
Shimoyama
Hideki
H
Watanabe
Shozo
S
Miyazaki
Antony
A
D'Emanuele
David
D
Attwood
D000082:Acetaminophen / Q000008:administration & dosage* / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D000284:Administration, Oral; D000464:Alginates / Q000737:chemistry*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001682:Biological Availability; D003680:Deglutition Disorders; D003692:Delayed-Action Preparations; D004058:Diffusion; D005079:Excipients / Q000737:chemistry; D005782:Gels / Q000737:chemistry; D005936:Glucans / Q000737:chemistry; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D010368:Pectins / Q000737:chemistry; D019999:Pharmaceutical Solutions; D051381:Rats; D017208:Rats, Wistar; D012212:Rheology; D014783:Viscosity; D014990:Xylans / Q000737:chemistry*
D000464:Alginates; D018712:Analgesics, Non-Narcotic; D003692:Delayed-Action Preparations; D005079:Excipients; D005782:Gels; D005936:Glucans; D006603:Hexuronic Acids; D019999:Pharmaceutical Solutions; D014990:Xylans; D000082:Acetaminophen; C029353:xyloglucan; D010368:Pectins; D020723:Glucuronic Acid