The influence of gastric acidity and taste masking agent on in situ gelling pectin formulations for oral sustained delivery of acetaminophen.
Dilute solutions of pectin containing complexed calcium ions form gels when these ions are released in the acidic environment of the stomach. The aim of this study was to examine the influence of a variation of gastric pH and the addition of a taste masking agent on the gelation of the pectin solutions and on the in vitro and in vivo release of acetaminophen from the gels. Increase of pH above 2.5 and addition of 10% (w/v) D-sorbitol significantly affected the ability of 1.5% (w/v) pectin solutions to form coherent gels in vitro. Gelation of sorbitol-free formulations was observed at pH 1.2 and in vitro release of acetaminophen from the gels followed diffusion-controlled kinetics; in vitro gelation of these formulations, however, was incomplete at pH 3.0 resulting in poor sustained release characteristics. Inclusion of 10% (w/v) D-sorbitol in the formulations inhibited the in vitro gelation of the 1.5% (w/v) pectin sols and poor sustained release properties were noted from these formulations even at pH 1.2. The bioavailability of acetaminophen from gels formed in the stomach of gastric-acidity controlled rabbits following oral administration of the liquid formulations was not, however, significantly affected either by the inclusion of 10% (w/v) D-sorbitol or increase of pH to 3.6. Visual observation showed in situ gelation of 1.5% (w/v) pectin formulations containing D-sorbitol at pH 4.3 suggesting that normal variations of gastric acidity in the fasting state will have no effect on the bioavailability of acetaminophen when delivered using these formulations.
Itoh
Kunihiko
K
Faculty of Pharmaceutical Sciences, Health Science University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
Kubo
Wataru
W
Fujiwara
Mariko
M
Watanabe
Hideki
H
Miyazaki
Shozo
S
Attwood
David
D
D000082:Acetaminophen / Q000737:chemistry* / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry*; D005744:Gastric Acid / Q000737:chemistry* / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D005782:Gels; D006863:Hydrogen-Ion Concentration; D008297:Male; D010368:Pectins / Q000737:chemistry*; D011817:Rabbits; D012995:Solubility; D013012:Sorbitol / Q000737:chemistry*; D013649:Taste
D003692:Delayed-Action Preparations; D005079:Excipients; D005782:Gels; D000082:Acetaminophen; D013012:Sorbitol; D010368:Pectins