Evaluation of an enzyme-containing capsular shaped pulsatile drug deliverysystem

Purpose. To develop an enzymatically-controlled pulsatile drug release syst em based on an impermeable capsule body, which contains the drug and is clo sed by an erodible pectin/pectinase-plug. Methods. The plug was prepared by direct compression of pectin and pectinas e in different ratios. In addition to the disintegration times of the plugs , the lag times and the release profiles of the pulsatile system were deter mined as a function of pectin:enzyme ratio, the pH of the surrounding mediu m, and the addition of buffering or chelating agents. Results. The disintegration time of the plug, respectively the lag time pri or to the drug release was controlled by the pectin:enzyme ratio and the pl ug weight. The inclusion of a buffering agent within the plug lead to a plu g disintegration independent of the surrounding pH. The addition of Na-EDTA hindered the formation of non-soluble calcium pectinate in the presence of calcium ions in the environment. The addition of effervescent agents to th e capsule content resulted in a rapid emptying of the capsule content after plug degradation. Conclusions. A pulsatile drug delivery system based on an erodible pectin p lug containing a pectinolytic enzyme was developed. The drug release was co ntrolled by the enzymatic degradation and dissolution of pectin.