Monitoring of Cocrystal Dissociation during the Wet Granulation Process in the Presence of Disintegrants by Using Low-Frequency Raman Spectroscopy

The aim of this study was to evaluate the effect three coformers and five disintegrants in granulation formulation on dissociation cocrystal during process by monitoring wet with probe-type low-frequency Raman (LF-Raman) spectroscopy. As model cocrystals, paracetamol (APAP)-oxalic acid (OXA), APAP-maleic (MLA), APAP-trimethylglycine (TMG) were used. recipe containing cocrystals performed over time high-performance LF-Raman spectrometry rate calculated from results multivariate analysis spectra. decreased order APAP-TMG, APAP-OXA, APAP-MLA, showing same as observed Powder X-ray diffraction measurements. Furthermore, compare for recipes typical (two low-substitution hydroxypropyl cellulose (HPC), cornstarch (CSW), carmellose sodium (CMC), crospovidone (CRP)). APAP-OXA CSW, HPCs, CMC, CRP. This difference thought be due disintegration mechanism water absorption ratio, which expected affect behavior disintegrant surface granulation. These suggested that spectroscopy is useful monitor can relative stability between different formulations.