Sigmoidal release of indomethacin from pectin matrix tablets: effect of in situ crosslinking by calcium cations.

Sigmoidal release pattern is therapeutically beneficial for timed release and colonic drug delivery, and is always observed in coated systems. In this study, sigmoidal release from pectin matrix tablets with indomethacin as a model drug was investigated. The underlying mechanisms are calcium cation-induced in situ crosslinking that retard the initial drug release to a limited percentage. Power law equation n values were estimated for sigmoidal release profiles. Results indicated that calcium chloride incorporated in pectin matrix functioned as retarding mechanisms on drug release. Larger amount of calcium chloride led to slower drug release and matrix erosion. Even at extremely high levels, retarding on drug release and matrix erosion rate was obvious, which highlighted the effect of calcium-induced in situ crosslinking as calcium chloride was a freely water-soluble salt. The sigmoidal release profiles were characterized by power law equation with high correlation coefficients of about 0.99 or over. Power law n values increased up to as high as 1.20 when calcium chloride content kept increasing. Erosion correlated well with release in almost all pectin matrix tablets indicating erosion-controlled mechanisms. It is concluded that large amount of calcium induces in situ crosslinking of pectin matrix and leads to sigmoidal release of indomethacin, and power law n values, sometimes larger than 1.0, are suitable to be used to describe sigmoidal release profiles.