I Krögel1, R Bodmeier. 1. College of Pharmacy, Freie Universität Berlin, Germany.
Abstract
PURPOSE: To develop an enzymatically-controlled pulsatile drug release system based on an impermeable capsule body, which contains the drug and is closed by an erodible pectin/pectinase-plug. METHODS: The plug was prepared by direct compression of pectin and pectinase in different ratios. In addition to the disintegration times of the plugs, the lag times and the release profiles of the pulsatile system were determined as a function of pectin:enzyme ratio, the pH of the surrounding medium, and the addition of buffering or chelating agents. RESULTS: The disintegration time of the plug, respectively the lag time prior to the drug release was controlled by the pectin:enzyme ratio and the plug weight. The inclusion of a buffering agent within the plug lead to a plug disintegration independent of the surrounding pH. The addition of N(alpha)-EDTA hindered the formation of non-soluble calcium pectinate in the presence of calcium ions in the environment. The addition of effervescent agents to the 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 plug containing a pectinolytic enzyme was developed. The drug release was controlled by the enzymatic degradation and dissolution of pectin.
PURPOSE: To develop an enzymatically-controlled pulsatile drug release system based on an impermeable capsule body, which contains the drug and is closed by an erodible pectin/pectinase-plug. METHODS: The plug was prepared by direct compression of pectin and pectinase in different ratios. In addition to the disintegration times of the plugs, the lag times and the release profiles of the pulsatile system were determined as a function of pectin:enzyme ratio, the pH of the surrounding medium, and the addition of buffering or chelating agents. RESULTS: The disintegration time of the plug, respectively the lag time prior to the drug release was controlled by the pectin:enzyme ratio and the plug weight. The inclusion of a buffering agent within the plug lead to a plug disintegration independent of the surrounding pH. The addition of N(alpha)-EDTA hindered the formation of non-soluble calcium pectinate in the presence of calcium ions in the environment. The addition of effervescent agents to the 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 plug containing a pectinolytic enzyme was developed. The drug release was controlled by the enzymatic degradation and dissolution of pectin.