Mechanodegradation of polymers: a limiting factor of mechanochemical activation in the production of amorphous solid dispersions by cryomilling

In this study we report on the influence of mechanochemical activation on the chemical stability of amorphous solid dispersions made up of indomethacin and HPMC, PVP, PVPVA or Soluplus®. In agreement with our recently published work, all applied carriers were found to be prone to chemical degradation. Covalent bonds within the polymers were cleaved and mechano-radicals were generated. Furthermore, decomposition of indomethacin was also observed but occurred only in presence of polymers. Hence, it is proposed that the generated mechano-radicals from the polymers are responsible for the chemical degradation of indomethacin. Our study also strongly suggests the existence of a critical polymer- and process-dependent molecular weight limit “M∞“ below which only limited mechano-degradation takes place since the lower molecular weight polymer PVP K12PF had a less profound influence on the degradation of indomethacin in comparison to PVP K25. Continue on mechanodegration of polymers

Keywords: Amorphous solid dispersions (ASD), cryomilling, polymers, chemical degradation, mechanochemical activation, radical scavenging, Kollidon 30, Kollidon 12PF (Polyvinylpyrrolidone (PVP), Kollidon VA 64 (Polyvinylpyrrolidone vinylacetate 124 (PVPVA),  Soluplus® (polyvinyl caprolactam – polyvinyl acetate – polyethylene glycol graft 125 copolymer), HPMC