Effect of coating of aluminum carboxymethylcellulose beads on the release and bioavailability of diclofenac sodium

Abstract

The production of spheres loaded with diclofenac sodium by the cross linking technique was achieved. The hydrophilic polymer sodium carboxymethylcellulose (Na-CMC) which gels in the presence of a cross linking agent, aluminum chloride (AlCl3), was used as a matrix forming agent for the bead production. To obtain a regular and uniform rate of drug release, the produced beads were coated with sodium alginate to increase the pathway of the diffused medium. Two processing variables were studied, the flocculating agent concentration (20, 40 and 60% w/v) and different coating times (15, 30 and 60 min). The results show that the higher concentrations of aluminum chloride (40 and 60% w/v) produced more uniform and rounded beads than that prepared using 20% w/v salt. The particle size of the core beads decreased insignificantly (P > 0.05) as the flocculating agent concentration increased. The coating time did not affect the particle size of the coated beads within the same concentration of aluminum chloride. The dissolution studies showed that the release rate of diclofenac sodium from the core beads increased with the increase of AlCl3 concentration and that the rate of drug release was markedly reduced after the coating of the core beads with Na-alginate. The results also show a linear relationship for drug release over a 4–5 h period from the core beads where it showed a longer straight line relationship (7 h) for the coated beads. The coating of the Al-CMC beads, prepared using 60% w/v AlCl3 · 6H2O, with 2% w/v aqueous solution of Na-alginate resulted in a significant (P < 0.05) sustaining action of the Al-CMC beads as indicated by the shift in Tmax from 1.7 ± 0.84 to 3 ± 0.71 h and the prolongation of the MRT from 7.86 ± 0.54 to 10.82 ± 1.33 h. The Cmax increased significantly from 5.43 ± 2.91 to 11.66 ± 6.18 μg/ml while the AUC0 → 24 increased insignificantly (P > 0.05) from 39.82 ± 26.61 to 57.92 ± 25.58 μg · h/ml resulting in a relative bioavailability of 145.45% relative to Al-CMC beads.