In this study, a method employing THz Raman imaging to characterize the solid state of acetaminophen within a solid dispersion prepared by hot melt extrusion was reported. The peak at 89 cm-1 originating from the crystalline lattice vibrations provides unambiguous discrimination between crystalline and amorphous N-acetyl-para-aminophenol (APAP; acetaminophen) contents in the hot melt extrusion (HME) extrudates. Extrudates from four different HME processes (two different temperatures and two levels of screw speeds) were analyzed and compared. The results show that both high process temperature and high screw speed favor the formation of amorphous APAP solid dispersions. Finally, the high spatial resolution (~ 1 μm) Raman images of the extrudates prepared at 170°C and 200 rpm show a near-complete amorphous APAP dispersion in an HPMC matrix, confirming an efficient HME process. The study demonstrates that THz Raman imaging is ideally suited for the identification of different solid physical states of the APIs in a polymer matrix, and provides direct visualization of their distribution in HME extrudates.
Keywords: acetaminophen; amorphous solid dispersion; hot melt extrusion; solid physical state; spatial resolution; terahertz raman imaging.