Tailor-made release triggering from hot-melt extruded complexes of basic polyelectrolyte and poorly water-soluble...

The aim of the study was the formulation of polyelectrolyte complexes composed of poorly water-soluble acid drugs and basic polymethacrylates by hot-melt extrusion enabling a tailor-made release pattern by the addition of inorganic salts. The influence of different electrolytes was analyzed at varying conditions in order to control drug delivery from the complexes. Poorly water-soluble model drugs naproxen and furosemide were applied in their non-ionic form. After hot-melt extrusion of the naproxen-polymethacrylate powder blend, XRPD and DSC measurements indicated the formation of a single-phase amorphous system. Milled extrudates were stable under storage at long-term and intermediate conditions. Polyelectrolyte complex formation by an acid-base reaction during hot-melt extrusion could be proven by the lack of vibrations of dimethylamino and carboxylic groups by FT-IR and Raman spectroscopy. The complexes did not dissolve in demineralized water. Drug release could be immediately induced by addition of neutral electrolytes. Tailor-made dissolution profiles were realized by controlled electrolyte triggering. Maximal effects were achieved by concentrations of 0.05-0.15 M NaCl. Different anions of alkali halogenides revealed variant magnitudes of the effect depending on the anion radius. Polyelectrolyte complex formation and dissolution principles were also confirmed for furosemide.