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

The aim of this study was to develop an extended-release tablet formulation using a new insitu cross-linking method. the effects of polyvalent cations on theophylline release from tabletsmade with the polyanionic polymers sodium alginate and sodium carboxymethylcellulose, wereinvestigated. different miliequivalents of the di and tri-valent cation, ca2+ and al3+, were addedto tablet formulations. the results of the dissolution study showed that incorporation of cationssustained the drug release. this is due to an in situ cross-linking between the polyanionicpolymers 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’ concentrationsand 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 extentin comparison with formulations containing each polymer alone. a zero-order drug releasekinetic 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.