In vitro evaluation and modification of pectinate gel beads containing trimethyl chitosan, as a multi-particulate system for delivery of water-soluble macromolecules to colon

Pectinate beads containing trimethyl chitosan chloride (TMC) as an absorption enhancer were prepared using Coomassie Brilliant Blue G 250 (CB) as a relatively high molecular weight water-soluble model drug. Effects of different formulation variables, such as cross-linker type, cross-linking time, cross-linker concentration, TMC: pectin ratio, pectin concentration and voltage of the bead generator, were assessed on in vitro bead characteristics by release and swelling-erosion studies. The bead formulation was optimized by factorial design. Some measures were taken to improve the bead characteristics and prolong their integrity during the gastrointestinal transit, such as biomineralization of the beads or coating them with high-methoxy pectin (PHM) or Eudragit L30-D 55 (EU). Possible CB-TMC complexation was investigated by Job's Plot method. The suitable system was obtained by coating the optimized core formulation with PHM or EU. TMC was found to form a complex with CB as a model anionic drug. Therefore, TMC-drug interactions can be used to modify the release characteristics of dosage forms. (c) 2005 Elsevier Ltd. All rights reserved.