The influence of variation of gastric pH on the gelation and release characteristics of in situ gelling pectin formulations.
The aim of this study was to examine the influence of variation of gastric pH over the range 1-3 on the gelation of liquid formulations of pectin and on the in vitro and in vivo release of paracetamol and ambroxol from the resultant gels. The formulations were dilute solutions of pectin containing complexed calcium ions that form gels when these ions are released in the acidic environment of the stomach. Gels suitable as vehicles for sustained delivery of these drugs were formed in vitro at pH<3 from pectin solutions of concentrations 1.0-2.0% (w/v). Very weak gels were formed at pH 3.0 resulting in poor sustained release characteristics compared with those at pH 1.2; no significant in vitro gelation was observed at pH 3.5. The bioavailabilities of paracetamol and ambroxol from gels formed in the stomach following oral administration of the liquid formulations were investigated using gastric-acidity controlled rabbits. Visual observations showed in situ gelation of 1.5% (w/v) pectin formulations under conditions of both high (pH 1.0-1.6) and low gastric acidity (pH 3.3-3.6). The bioavailabilities of these drugs were not significantly different when released from gels formed at the two pH limits suggesting that normal variations of gastric acidity in the fasting state will have no effect on the bioavailability of these drugs when delivered using this vehicle.
Itoh
Kunihiko
K
Faculty of Pharmaceutical Sciences, Health Science University of Hokkaido, Ishikari-Tohbetsu, Hokkaido 061-0293, Japan.
Kubo
Wataru
W
Fujiwara
Mariko
M
Hirayama
Tomohiro
T
Miyazaki
Shozo
S
Dairaku
Masatake
M
Togashi
Mitsuo
M
Mikami
Ryozo
R
Attwood
David
D
D000082:Acetaminophen / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D000551:Ambroxol / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D005750:Gastric Juice / Q000737:chemistry*; D005782:Gels; D006863:Hydrogen-Ion Concentration; D008297:Male; D010368:Pectins / Q000737:chemistry*; D011817:Rabbits; D012995:Solubility
D003692:Delayed-Action Preparations; D005782:Gels; D000551:Ambroxol; D000082:Acetaminophen; D010368:Pectins