Matrix tablets based on carrageenans with dual controlled release of doxazosin mesylate

The use of polymeric polyelectrolytes as matrix-forming agents is far from optimally or fully understood. Polyelectrolyte carrageenan (CARR) matrices loaded with oppositely charged active substance doxazosin mesylate (DM) were investigated according to their water-uptake/erosion properties, in situ complexation ability of CARR with DM, and the possibility to achieve dual drug release control. Interactions between different CARR types (ι-, κ-, and λ-) and DM were confirmed by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and zeta potential measurements. Combination of water-uptake/erosion with in situ complexation prolonged DM release from CARR matrices for more than 24 h. The rate order of drug release was in accordance with the number of ester sulfate moieties per disaccharide unit of CARRs (κ (1) > ι (2) > λ (3)). The higher the charge on the CARR backbone, the higher the number of interactions with DM and the slower the drug release. Low pH, more vigorous hydrodynamics, and higher ionic strength resulted in faster drug release. Based on zeta potential measurements of DM and CARRs, proposed influence of counterion condensation and its effect on screening polyelectrolyte–drug interactions was confirmed to lower in situ DM–CARR complexation. Dual drug release control from polyelectrolyte matrices by water-uptake/erosion and in situ complexation offers many new approaches for designing controlled-release systems.