N-acylated chitosan: Hydrophobic matrices for controlled drug release.

Abstract

Abstract 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.