Development of a bead-in-matrix delivery system for insulin
The oral route remains the most convenient and popular route for drug administration. However, for therapeutic peptide drugs, parenteral administration remains the most used route of administration as the use of the oral route for protein and peptide drugs being hindered by pre-systemic enzymatic degradation and low intestinal epithelial permeability. To overcome the low intestinal epithelial permeability, a safe and effective absorption enhancing agent can be included in the dosage form. Previous studies found that Aloe vera gel, sodium deoxycholate and N-trimethyl chitosan chloride (TMC) had the ability to increase drug transport across in vitro intestinal epithelial models. The aim of this study was to prepare a bead-in-matrix delivery system comprising of microbeads containing insulin loaded into macro-beads containing an absorption enhancer. Three different absorption enhancers, namely A. vera gel, sodium deoxycholate and TMC at two different concentration levels (0.5% and 1% w/w) were investigated. Based on the experimental variables, 18 bead-in-matrix formulations were prepared in total. The bead-in-matrix delivery systems were designed in such a way that the absorption enhancer in the macro-beads could reach the site of absorption first, in order to open the tight junctions to facilitate the paracellular transport of insulin contained in the micro-beads. The bead-in-matrix delivery systems were characterised in terms of insulin content (assay), weight variation, particle size, dissolution behaviour and the ability to deliver insulin across porcine intestinal tissue. Electron microscopy indicated that micro-beads could be successfully enclosed within macro-beads resulting in a bead-in-matrix delivery system. In an effort to investigate the possibility to limit insulin release and in effect protect it from an acidic environment, the bead-in-matrix delivery systems were successfully coated with a mixture of Eudragit® L100 and Eudragit® S100 to produce enteric coated delivery systems. Dissolution studies indicated that the enteric coating limited insulin release in an acidic environment and complete insulin release was illustrated at a pH of 6.8 within 150 min for all bead-in-matrix delivery systems. All the bead-in-matrix delivery systems exhibited similar drug release patterns. Transport data indicated that the absorption enhancers (i.e. A. vera gel, sodium deoxycholate and TMC) in all bead-in-matrix formulations successfully facilitated the paracellular transport of insulin. The most effective absorption enhancer in this study was A. vera gel.
- Health Sciences