Development of pectin matrix tablets for colonic delivery of model drug ropivacaine

The objective of this work was to develop pectin-based matrix tablets for colonic delivery of the model drug ropivacaine, with the future perspective of radiolabelling the system by neutron activation technique for a gamma-scintigraphic study. The aim was to investigate some formulation factors that could reduce the release of the drug in the simulated gastric and intestinal fluids, increase the release in the simulated cecal fluid (with pectinolytic enzymes) and improve the poor compactibility of pectins. For dissolution studies, the flow-through apparatus with sequential dissolution liquids simulating the mouth-to-colon conditions was used. The effect of two pectin types, the incorporation of ethylcellulose as a dry matrix-additive and water or ethanol as granulation liquids were investigated in a study designed as a D-optimal mixture. Amidated pectin (Am.P) produced harder tablets than the calcium salt of pectin (Ca.P) and was more susceptible to enzymatic degradation. Addition of ethylcellulose increased the tablet strength and the dissolution rate. Furthermore, directly compressed Am.P tablets were produced by addition of coarse or micronised qualities of ethylcellulose. The latter improved the crushing strength markedly imposing a marginal release-reducing effect. Coating this formulation with Eudragit(R) L 100 reduced the release in the simulated upper GI conditions without interference with the subsequent enzymatic activity. (C) 2000 Elsevier Science B.V. All rights reserved.