Electrolyte-stimulated biphasic dissolution profile and stability enhancement for tablets containing drug-polyelectrolyte complexes.

PURPOSE: Recently introduced drug-polyelectrolyte complexes prepared by hot-melt extrusion should be processed to solid dosage forms with tailor-made release properties. Their potential of stability enhancement should be investigated.
METHODS: Milled hot-melt extruded naproxen-EUDRAGIT® E PO polyelectrolyte complexes were subsequently processed to double-layer tablets with varying complex loadings on a rotary-die press. Physicochemical interactions were studied under ICH guideline conditions and using the Gordon-Taylor equation. Sorption and desorption were determined to investigate the influence of moisture and temperature on the complex and related to stability tests under accelerated conditions.
RESULTS: Naproxen release from the drug-polyelectrolyte complex is triggered by electrolyte concentration. Depending on the complex loading, phosphate buffer pH 6.8 stimulated a biphasic dissolution profile of the produced double-layer tablets: immediate release from the first layer with 65% loading and prolonged release from the second layer within 24 h (98.5% loading). XRPD patterns proved pseudopolymorphism for tablets containing the pure drug under common storage conditions whereas the drug-complex was stable in the amorphous state.
CONCLUSIONS: Drug-polyelectrolyte complexes enable tailor-made dissolution profiles of solid dosage forms by electrolyte stimulation and increase stability under common storage conditions.