Are chitosan formulations mucoadhesive in the human small intestine? An evaluation based on gamma scintigraphy.
Rapid passage through the proximal intestine can result in the low bioavailability of a drug substance with site-specific absorption characteristics in the upper gastrointestinal tract. To overcome this, there is increasing interest in developing gastro-retentive formulations and/or formulations that linger in the proximal parts of the small intestine, e.g. by using mucoadhesive polymers as excipients in formulations. In our recent study, we used neutron activation-based gamma scintigraphy to evaluate the gastro-retentive properties of formulations containing chitosan (Mw 150 kDa) in man. At the same time, we had an opportunity to monitor the transit of the formulations (40 or 95% of chitosan) in the small intestine. Gamma scintigraphic investigations revealed that although the chitosan studied had exhibited marked mucoadhesive capacities in vitro, retention of the chitosan formulations in the upper gastrointestinal tract was not sufficiently reproducible and the duration of retention was relatively short. In 3 volunteers out of 10, the formulation adhered to the gastric mucosa (retention times varied from 1.25 to 2.5 h) and in two volunteers to the upper small intestine (approximate retention time 45 min). In one case, the formulation adhered to the oesophagus. The system failed to increase the bioavailability of furosemide, a drug site-specifically absorbed in the upper gastrointestinal tract. As far as the kind of formulation studied is concerned, preparation of a system that is site-specific to the stomach and/or the upper small intestine seems difficult if the proposed mechanism of action is mucoadhesion. The results suggest that other mechanisms of action should also be studied.
Säkkinen
Mia
M
Division of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FI-00014 University of Helsinki, Finland. mia.sakkinen@helsinki.fi
Marvola
Janne
J
Kanerva
Hanna
H
Lindevall
Kai
K
Ahonen
Aapo
A
Marvola
Martti
M
D000268:Adhesiveness; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics*; D005079:Excipients / Q000737:chemistry; D005665:Furosemide / Q000008:administration & dosage / Q000493:pharmacokinetics; D015902:Gamma Cameras; D005753:Gastric Mucosa / Q000000981:diagnostic imaging / Q000378:metabolism; D005772:Gastrointestinal Transit; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000000981:diagnostic imaging / Q000378:metabolism*; D007421:Intestine, Small / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D011849:Radioactive Tracers; D011877:Radionuclide Imaging; D012493:Samarium; D012588:Scintillation Counting; D013997:Time Factors
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005079:Excipients; D011849:Radioactive Tracers; D012493:Samarium; D005665:Furosemide; D048271:Chitosan