Indomethacin release from ion-exchange microspheres: impregnation with alginate reduces release rate.

ABSTRACT

Ion-exchange microspheres (MS) designed as a drug delivery system for embolization coupling ability to occlude vessels and chemotherapy were used to evaluate a manufacturing process allowing to control the drug release rate through reduction of diffusion rate of the drug within the particle by impregnation of calcium alginate inside the porous MS. Impregnation was performed by diffusion of sodium alginate inside DEAE-Trisacryl(R) MS, dispersion of the MS in deionised water and gelling alginate by adding CaCl(2) to the dispersed MS. Studied parameters were alginate concentration, alginate diffusion time and calcium concentration. Indomethacin was loaded into the MS by eluting an aqueous indomethacin solution through a chromatographic column packed with impregnated MS. Indomethacin loading was reduced by alginate. Swelling studies showed indomethacin loading enhanced the hydrophobicity of MS while impregnation had no effect. This had an incidence on indomethacin release rate, which was assessed using the rapid elution of PBS through loaded impregnated MS packed in a column. Indomethacin loading reduced its own rate of release. MS impregnated with 2% w/v alginate gelled with a 40 mM calcium solution presented the lower release rate. This work indicated the manufacturing conditions to display a calcium alginate matrix effect on indomethacin release from DEAE-Trisacryl MS.