Gamma scintigraphic evaluation of the fate of microcrystalline chitosan granules in human stomach.
In several reports of in vitro studies it has been suggested that the mucoadhesive chitosans could be of value in preparing gastro-retentive formulations. The aim of this study was to obtain direct in vivo evidence of whether microcrystalline chitosan (MCCh) formulations acted as gastro-retentive systems in humans. Neutron-activation-based gamma scintigraphy was used to study gastric residence times of MCCh granules in healthy male volunteers. Possible effects of neutron irradiation on the properties of the MCCh granules were studied in advance, in vitro. In vivo gamma scintigraphic evaluations were carried out with the subjects in a fasted state, using granules containing 95% (F1) or 40% (F2) of MCCh of molecular weight 150 kDa. Reference formulation (F3) was lactose granules. The reference granules passed rapidly from the stomach (mean t50% 0.5+/-0.3 h (n=5)). MCCh in granules prolonged gastric residence times of the formulations in only a few cases (in one volunteer in the F1 group (n=4) and in two volunteers in the F2 group (n=5)). Maximum individual t50% values were 2.1 h (F1) and 2.3 h (F2). It was concluded that the in vivo mucoadhesion of MCCh formulations is erratic, and that the formulations studied are not reliable gastro-retentive drug delivery systems.
Säkkinen
Mia
M
Division of Biopharmaceutics and Pharmacokinetics, Department of Pharmacy, University of Helsinki, Helsinki, Finland. mia.sakkinen@helsinki.fi
Marvola
Janne
J
Kanerva
Hanna
H
Lindevall
Kai
K
Lipponen
Maija
M
Kekki
Tommi
T
Ahonen
Aapo
A
Marvola
Martti
M
D000328:Adult; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000528:radiation effects*; D003460:Crystallization / Q000379:methods*; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004341:Drug Evaluation / Q000379:methods*; D005720:Gamma Rays; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D009501:Neutron Activation Analysis / Q000379:methods; D011868:Radioisotopes / Q000008:administration & dosage / Q000737:chemistry; D011877:Radionuclide Imaging; D012493:Samarium / Q000008:administration & dosage / Q000737:chemistry
D003692:Delayed-Action Preparations; D011868:Radioisotopes; D012493:Samarium; D048271:Chitosan