Characterization of the Solid Physical State of API and Its Distribution in Pharmaceutical Hot Melt Extrudates Using Terahertz Raman Imaging
- 40 Downloads
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.
Keywordshot melt extrusion terahertz raman imaging acetaminophen solid physical state amorphous solid dispersion spatial resolution
- 1.Repka MA, Bandari S, Kallakunta VR, Vo AQ, McFall H, Pimparade MB, et al. Melt extrusion with poorly soluble drugs—an integrated review. Int J Pharm. 2018;535:68–85. https://doi.org/10.1016/j.ijpharm.2017.10.056.
- 2.Censi R, Gigliobianco MR, Casadidio C, Di Martino P. Hot melt extrusion: highlighting physicochemical factors to be investigated while designing and optimizing a hot melt extrusion process. Pharmaceutics. 2018;10:89. https://doi.org/10.3390/pharmaceutics10030089.
- 3.Baghel S, Cathcart H, O’Reilly NJ. Polymeric amorphous solid dispersions: a review of amorphization, crystallization, stabilization, solid-state characterization, and aqueous solubilization of biopharmaceutical classification system class II drugs. J Pharm Sci. 2016;105:2527–44. https://doi.org/10.1016/j.xphs.2015.10.008.CrossRefPubMedGoogle Scholar
- 6.Parrott EPJ, Zeitler JA. Terahertz time-domain and low-frequency Raman spectroscopy of organic materials. Appl Spectrosc. 2015;69:1–25. https://doi.org/10.1366/14-07707.