Ionotropic gelation: encapsulation of indomethacin in calcium alginate gel discs

Ionotropic gelation by divalent metal interaction was employed as an approach to design a modified release multiple-unit oral drug-delivery system. This process was achieved by crosslinking an indomethacin-sodium alginate dispersion with calcium ions to induce the spontaneous formation of indomethacin-calcium alginate gel discs. A significant part in the validation of the integrity of the system, involved a preformulatory stage for the optimization of the curing conditions and potency determination of the gel discs. A three-phase approach was developed to establish the critical curing parameters. Since curing involved crosslinking of the sodium alginate with calcium ions, an optimal concentration of calcium chloride (phase one) and crosslinking reaction-time (phase two) had to be determined. Furthermore, the third phase involved the optimization of the air-drying time of the gel discs. In phases one and two, stabilization of in vitro drug-release characteristics was used as the marker of optimal crosslinking efficiency. Phase three was based on achieving fully dried gel discs by drying to constant weight at 21 degrees C under an extractor. The study revealed that optimal crosslinking efficiency was achieved in 1%w/v calcium chloride solution for 24 h and air-dried at 21 degrees C under an extractor for 48 h. The three solvent/solution systems investigated for their ability to liberate completely the drug from the matrix system were methanol, sodium citrate (1%w/v) and phosphate buffer pH 6.2. Phosphate buffer provided optimal drug removal, in addition to its ability to induce swelling of the calcium alginate gel discs. Furthermore, drug loading also increased with the use of increasing concentrations of sodium alginate in the formulations.