INTERACTION OF INDOMETHACIN WITH LOW-MOLECULAR-WEIGHT CHITOSAN, AND IMPROVEMENTS OF SOME PHARMACEUTICAL PROPERTIES OF INDOMETHACIN BY LOW-MOLECULAR-WEIGHT CHITOSANS

The interaction of four kinds of low molecular weight chitosans, which were different in molecular weight and degree of deacetylation, were studied in solution and the solid state using an anti-inflammatory drug, indomethacin (IM), as an acidic model molecule. The solubility of IM enhanced with increasing concentration of low molecular weight chitosan, especially C-I which had the lowest molecular weight and least degree of deacetylation. The C-I crystal complex was obtained in a molar ratio of 16:1 (IM : C-I) from aqueous solution. The data suggested that the acetyl group and amino group of chitosan played an important role in the complexation. The IM dissolution rates from kneaded mixtures with low molecular weight chitosans were enhanced in the order of C-I >> C-II > C-III > C-IV (molecular weight: C-IV > C-III > C-II > C-I). The oral absorption rate of IM from C-I kneaded mixture was improved compared with IM alone.