N-acylated chitosan: hydrophobic matrices for controlled drug release.
N-acylation of chitosan with various fatty acid (C(6)-C(16)) chlorides increased its hydrophobic character and made important changes in its structural features. Unmodified chitosan exhibited a low degree of order (DO) and a weak tablet crushing strength. Chitosan acylated with a short chain length (C(6)) possessed similar properties, but exhibited significant swelling. Acylation with longer side chains (C(8)-C(16)) resulted in a higher DO and crushing strength but lower swelling. The best mechanical characteristics and drug release properties were found for palmitoyl chitosan (substitution degree 40-50%) tablets with 20% acetaminophen as a tracer. The high stability of these monolithic tablets appears to be due to hydrophobic interactions between side chains, as shown by a more organized structure. Infrared spectroscopy, X-ray diffractometry and proton nuclear magnetic resonance analyses of palmitoyl chitosan were consistent with a hydrophobic self-assembling model. Drug dissolution kinetics showed longer release times for higher degrees of functionalization, i.e. 30 h (for 47% substitution) and 90 h (for 69% substitution), suggesting palmitoyl chitosan excipients as interesting candidates for oral and subdermal pharmaceutical applications.
Le Tien
Canh
C
Department of Chemistry and Biochemistry, Université du Québec à Montréal, CP 8888, Succ Centre-Ville, Montréal, Quebec, Canada H3C 3P8.
Lacroix
Monique
M
Ispas-Szabo
Pompilia
P
Mateescu
Mircea-Alexandru
MA
D000215:Acylation; D002686:Chitin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000493:pharmacokinetics*; D048271:Chitosan; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000493:pharmacokinetics*; D057927:Hydrophobic and Hydrophilic Interactions; D012995:Solubility; D013607:Tablets
D003692:Delayed-Action Preparations; D013607:Tablets; D002686:Chitin; D048271:Chitosan