Long-term stable hydrogels for biorelevant dissolution testing of drug-eluting stents

Background: For the purpose of biorelevant dissolution testing hydrogels have recently been used to investigate release and distribution behavior of drugs released from specialized dosage forms such as drug-eluting stents. For stent testing using the vesselsimulating flow-through cell (vFTC) certain functional properties regarding life time of the used hydrogels such as hardening/ softening, degradation/erosion and swelling/shrinkage during the time period of dissolution testing are of highest interest. Methods: Hydrogels composed of alginate, agar, agarose, polyacrylamide (PAA) and poly(vinyl alcohol) (PVA) were prepared using physical and chemical cross-linking methods. To characterize the mechanical stability of the test specimens stress-strain curves were recorded by texture analysis before and after perfusion in the vFTC for 28 days and Young’s moduli were calculated. The surface morphology of the test specimens was examined using scanning electron microscopy. Water uptake upon incubation was determined. Results: Besides the previously established alginate gels, suitable hydrogels consisting of 2 wt% agar, 2 wt% agarose, 10 wt% PAA or 15 wt% PVA were identified. Comparison of stress-strain curves indicated a sample softening of reference as well as agar and a slight hardening of PVA whereas hardness of agarose and PAA remained unchanged. Young’s moduli of agarose and PAA were almost unaffected after 28 days of perfusion. Swelling of PAA by 18 wt% and shrinkage of PVA by 14 wt% was observed compared to agar and agarose whose water uptake was negligibly small. Conclusion: The hydrogels differ not only in their preparation procedure but also regarding their swelling properties, surface morphology and texture. Due to the ease of handling, mild gelling conditions, no swelling tendencies, elastic properties, and nearly unaffected texture after 28 days of perfusion compared to native test specimens, agarose gels are considered as the best choice for longterm testing using the vFTC.