IONOTROPIC GELATION - ENCAPSULATION OF INDOMETHACIN IN CALCIUM ALGINATE GEL DISCS

Ionotropic gelation by divalent metal interaction was employed as an a pproach to design a modified release multiple-unit oral drug-delivery system. This process was achieved by crosslinking an indomethacin-sodi um alginate dispersion with calcium ions to induce the spontaneous for mation of indomethacin-calcium alginate gel discs. A significant part in the validation of the integrity of the system, involved a preformul atory stage for the optimization of the curing conditions and potency determination of the gel discs. A three-phase approach was developed t o establish the critical curing parameters. Since curing involved cros slinking of the sodium alginate with calcium ions, an optimal concentr ation 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 o ne and two, stabilization of in vitro drug-release characteristics was used as the marker of optimal crosslinking efficiency. Phase three wa s based on achieving fully dried gel discs by drying to constant weigh t at 21 degrees C under an extractor. The study revealed that optimal crosslinking efficiency was achieved in 1 %w/v calcium chloride soluti on 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, sod ium citrate (1 %w/v) and phosphate buffer pH 6.2. Phosphate buffer pro vided optimal drug removal, in addition to its ability to induce swell ing of the calcium alginate gel discs. Furthermore, drug loading also increased with the use of increasing concentrations of sodium alginate in the formulations.