In vivo evaluation of matrix granules containing microcrystalline chitosan as a gel-forming excipient.
Interest in drug delivery to the gastrointestinal tract by means of chitosan has been increasing. In the study reported, the biopharmaceutical properties of granules containing microcrystalline chitosan (MCCh; molecular weight 150 kDa, degree of deacetylation 75%) were evaluated via bioavailability tests in human volunteers. Ibuprofen and furosemide were used as model drugs. With ibuprofen, granules containing 40% of MCCh behaved as a slow-release formulation (t(max) 2.9 h). With furosemide, the most marked difference between a conventional dosage form and granules containing 40% MCCh was a marked lag time (0.5 h) before absorption from the latter. This difference was reflected in t(max) values for furosemide. Despite the lag time, AUC values for furosemide were high, indicating that the granules containing MCCh had remained in the stomach and that drug release had taken place in the stomach rather than in the intestine. The results of the bioavailability studies indicate that MCCh matrix granules allow a simple preparation of slow-release and perhaps stomach-specific dosage forms. Use of model drugs differing in relation to sites of absorption in the gastrointestinal tract aided identification of sites of absorption of drugs from the granules. Further studies, including gamma-scintigraphic evaluations, will be performed on how the granules behave in the stomach.
Säkkinen
M
M
Department of Pharmacy, Division of Biopharmaceutics and Pharmacokinetics, University of Helsinki, P.O. Box 56, FIN-00014 Helsinki, Finland. mia.sakkinen@helsinki.fi
Linna
A
A
Ojala
S
S
Jürjenson
H
H
Veski
P
P
Marvola
M
M
D000328:Adult; D001682:Biological Availability; D002686:Chitin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000737:chemistry; D048271:Chitosan; D018592:Cross-Over Studies; D005079:Excipients / Q000008:administration & dosage*; D005665:Furosemide / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D005753:Gastric Mucosa / Q000378:metabolism; D005782:Gels; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
D005079:Excipients; D005782:Gels; D002686:Chitin; D005665:Furosemide; D048271:Chitosan; D007052:Ibuprofen