The use of scintigraphy to provide "proof of concept" for novel polysaccharide preparations designed for colonic drug delivery.
OBJECTIVE
The aim of the present study was to provide "proof of concept" data in man for novel polysaccharide preparations designed for colonic drug delivery using gamma scintigraphy.


METHODS
Two placebo calcium pectinate matrix tablet formulations were studied: one contained calcium pectinate and pectin (CaP/P) and was designed to rapidly disintegrate in the ascending colon, the other contained calcium pectinate and guar gum (CaP/GG) and was designed to disintegrate more slowly, releasing its contents throughout the ascending and transverse colon. Both formulations were enteric coated in order to protect them from the stomach. Ten healthy volunteers received either a CaP/P or CaP/GG tablet, in a randomised cross-over study. Transit and disintegration of the radiolabelled formulations was followed by gamma scintigraphy. Rat studies were conducted in order to verify that the expected colonic degradation of the polysaccharide formulations was as a consequence of bacterial enzyme attack.


RESULTS
The in vivo clinical study confirmed the results obtained in the rat and bench in vitro fermentation models; complete tablet disintegration for Formulation CaP/GG appeared to be slower than that of Formulation CaP/P and the time and the location of complete tablet disintegration was more reproducible with Formulation CaP/P compared to Formulation CaP/GG.


CONCLUSIONS
These results provide "proof of concept" data for the use of calcium pectinate preparations for drug delivery to the colon and highlight the value of scintigraphy in focusing the development strategy for colonic targeting preparations.
Adkin
D A
DA
Pharmaceutical Profiles Limited, Highfields Science Park, Nottingham, UK.
Kenyon
C J
CJ
Lerner
E I
EI
Landau
I
I
Strauss
E
E
Caron
D
D
Penhasi
A
A
Rubinstein
A
A
Wilding
I R
IR
D000328:Adult; D000818:Animals; D018592:Cross-Over Studies; D016503:Drug Delivery Systems; D005260:Female; D005685:Galactans; D005772:Gastrointestinal Transit; D006801:Humans; D007080:Ileocecal Valve / Q000000981:diagnostic imaging; D007553:Isotope Labeling; D008297:Male; D008351:Mannans; D008875:Middle Aged; D010368:Pectins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D053149:Plant Gums; D011877:Radionuclide Imaging; D051381:Rats; D013270:Stomach / Q000000981:diagnostic imaging; D013608:Tablets, Enteric-Coated
D005685:Galactans; D008351:Mannans; D053149:Plant Gums; D013608:Tablets, Enteric-Coated; D010368:Pectins; C007894:guar gum; C003181:polygalacturonic acid