In vitro evaluation of microcrystalline chitosan (MCCh) as gel-forming excipient in matrix granules.
Although much research has been carried out into the effects of chitosan and its chemical properties on drug release, less attention has been paid to the effects of its physical properties. The aim of this study was to characterize microcrystalline chitosan (MCCh) as a gel-forming excipient. Matrix granules containing chitosans of differing physicochemical properties (crystallinity, molecular weight, degree of deacetylation) and ibuprofen or paracetamol as model drugs were prepared. Gel formation by the chitosans in the granules and subsequent effects on drug release were studied at pH 1.2 and pH 5.8. The chitosan granules acted as slow-release formulations in the case of ibuprofen (a class-II drug in the Biopharmaceutics Classification System) but with paracetamol (class-I) no controlled-release formulation could be developed. Microcrystalline grades of chitosan had the most marked retardant effects on drug release, with the efficacy of gel formation by MCCh explaining the results. The kinetic constant for ibuprofen release (at pH 5.8) ranged from 22%.h(-1) (MCCh) to 31%.h(-1) (unmodified chitosan). The release rate was easily controlled by varying the amount or molecular weight of MCCh, and to a lesser extent by the degree of deacetylation. The effects were most pronounced when pH was markedly acidic, suggesting that MCCh granules might be particularly useful in preparing stomach-specific slow-release dosage forms.
Säkkinen
Mia
M
Division of Biopharmaceutics and Pharmacokinetics, Department of Pharmacy, University of Helsinki, PO Box 56, FIN-00014 Helsinki, Finland. mia.sakkinen@helsinki.fi
Seppälä
Ulrika
U
Heinänen
Paula
P
Marvola
Martti
M
D002626:Chemistry, Pharmaceutical; D002686:Chitin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000493:pharmacokinetics*; D048271:Chitosan; D003460:Crystallization; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005079:Excipients / Q000737:chemistry* / Q000493:pharmacokinetics*; D005782:Gels; D008863:Microspheres
D005079:Excipients; D005782:Gels; D002686:Chitin; D048271:Chitosan