In Situ Cross-Linking of Polyanionic Polymers to Sustain the Drug Release from Theophylline Tablets

Abstract

The aim of this study was to develop an extended-release tablet formulation using a new in situ cross-linking method. The effects of polyvalent cations on theophylline release from tablets made with the polyanionic polymers sodium alginate and sodium carboxymethylcellulose, were investigated. Different miliequivalents of the di and tri-valent cation, Ca 2+ and Al 3+ , were added to tablet formulations. The results of the dissolution study showed that incorporation of cations sustained the drug release. This is due to an in situ cross-linking between the polyanionic polymers and the added cation in tablet formulation. The drug release prolongation and the release kinetics were dependent on the nature of the polymers and the cations’ concentrations and valences. The drug release rate decreased by an increase in cation concentration. The combination of the two investigated polymers decreased the drug release rate to a higher extent in comparison with formulations containing each polymer alone. A zero-order drug release kinetic was observed in formulations containing 1:1:1 ratio of drug: Na alginate: NaCMC, and the investigated cations. These results showed that the in situ cross-linking by polyanionic polymers can be used for controlling the drug release rate.