The influence of the degree of esterification on the release characteristics of in situ gelling pectin formulations for oral sustained delivery of paracetamol.
The aim of this study was to examine the effect of a change of the degree of esterification of pectin on the in situ gelation and release characteristics of 1.5% (w/v) pectin solutions over a wide pH range. Formulations of pectin with degrees of esterification of 9% (DE9) and 31% (DE31) containing complexed calcium ions formed gels in vitro at pH 1.2 as a consequence of cross-linking of the pectin chains by free calcium ions released from the complex. In vitro release of paracetamol from these gels was diffusion controlled. A sustained release of paracetamol was observed following oral administration of pectin DE9 and DE31 formulations to gastric acidity-controlled rats at pH 2.5 but only with DE9 formulations at pH 5.5. Examination of the stomach contents confirmed effective in situ gelation of pectin DE9 formulations at a gastric pH of 6 but there was no evidence of the gelation of pectin DE31 formulations at this pH.
Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido, Japan.
Shozo
S
Miyazaki
Hanae
H
Murofushi
Tetsuya
T
Shimoyama
Kunihiko
K
Itoh
Michiya
M
Kobayashi
David
D
Attwood
D000082:Acetaminophen / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D000284:Administration, Oral; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry; D004058:Diffusion; D016503:Drug Delivery Systems; D004951:Esterification; D005753:Gastric Mucosa / Q000378:metabolism; D005782:Gels / Q000008:administration & dosage / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008297:Male; D010368:Pectins / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar
D003692:Delayed-Action Preparations; D005782:Gels; D000082:Acetaminophen; D010368:Pectins; D002118:Calcium