V. Pillay et al., IONOTROPIC GELATION - ENCAPSULATION OF INDOMETHACIN IN CALCIUM ALGINATE GEL DISCS, Journal of microencapsulation, 15(2), 1998, pp. 215-226
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.