Electrolyte-stimulated biphasic dissolution profile and stability enhancement for tablets containing drug-polyelectrolyte complexes.
OBJECTIVE
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.
Heinrich Heine University Duesseldorf, Duesseldorf, Germany. christoph.kindermann@uni-duesseldorf.de
Christoph
C
Kindermann
Karin
K
Matthée
Frank
F
Sievert
Jörg
J
Breitkreutz
D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry; D004304:Dosage Forms; D004355:Drug Stability; D004573:Electrolytes / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D009288:Naproxen / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility; D013607:Tablets / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods
D003692:Delayed-Action Preparations; D004304:Dosage Forms; D004573:Electrolytes; D004364:Pharmaceutical Preparations; D013607:Tablets; D009288:Naproxen