Oral sustained delivery of theophylline and cimetidine from in situ gelling pectin formulations in rabbits.
The aim of this study was to evaluate the potential of an in situ gelling pectin formulation as a vehicle for the oral sustained delivery of theophylline and cimetidine. In vitro studies demonstrated diffusion-controlled release of theophylline from 1, 1.5, and 2% w/v pectin gels. Release of this drug from 1.5% w/v pectin gels formed in situ in rabbit stomach was sustained over a period of 12 hours giving a theophylline bioavailability some seven fold higher than when administered from a commercial syrup. In contrast, interactions between cimetidine and pectin led to weak gelation of the pectin sols that prevented any meaningful determination of in vitro release characteristics. Similarly, in vivo release profiles from pectin formulations containing cimetidine were similar to that from a solution of this drug in buffer, indicative of weak gelation. Examination of the content of the rabbit stomach 5 hours after administration of 1.5% w/v pectin sols containing drug confirmed gel formation, but gels containing cimetidine were noticeably softer than those containing theophylline.
Kubo
Wataru
W
Faculty of Pharmaceutical Sciences, Health Science University of Hokkaido, Hokkaido, Japan.
Itoh
Kunihiko
K
Miyazaki
Shozo
S
Attwood
David
D
D000284:Administration, Oral; D000818:Animals; D002927:Cimetidine / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D005750:Gastric Juice / Q000737:chemistry; D005782:Gels; D008297:Male; D010368:Pectins / Q000737:chemistry*; D011817:Rabbits; D013806:Theophylline / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics
D003692:Delayed-Action Preparations; D005782:Gels; D002927:Cimetidine; D010368:Pectins; D013806:Theophylline