Microwave-assisted forced degradation using high-throughput microtiter platforms.

Parallel microwave-assisted forced degradation in sealed HPLC/GC vials utilizing a high-throughput platform is described. The platform is made out of strongly microwave absorbing silicon carbide (SiC) plates providing 20 bore holes having the appropriate dimensions to be fitted with standard autosampler HPLC/GC vials serving as reaction vessels. Due to the possibility of heating up to four SiC platforms simultaneously (80 reactions) in a dedicated multimode microwave cavity with online temperature control, efficient parallel forced degradation studies can be performed at temperatures and pressures of up to 200 °C and 20 bar, respectively. Since degradation reactions and analyses are performed in the same vessel, the sample handling effort is reduced and errors caused by a required transfer step are avoided. As proof-of-concept, the platform was evaluated for the parallel testing of various stress conditions on the drug indomethacin. The obtained data provided a rapid overview over suitable stress conditions at high temperatures, implicating a significant reduction in time required for the forced degradation compared to conventional methods at room temperature. Applying acidic (0.01-0.1 M HCl, 1-15 M AcOH), basic (0.001-0.01 M NaOH, 0.001-0.01 M NaHCO(3)) and oxidative (0.001-0.02% H(2)O(2)) stress conditions at 150 °C for 5 min resulted in similar indomethacin degradation levels requiring 0.5-20 h at lower temperatures (25-100 °C). In addition solvent stability tests exposing indomethacin to 20 different, mostly organic, solvents at 150 °C and 160 °C for 30 min and the exposure of the solid drug to various gases (N(2), Ar, O(2), NH(3), air), applying high temperatures are presented.