H. Wu1 , E. J. Heilweil2 , A. S. Hussain3 , M. A. Khan1 , 1Division of Product Quality Research, OTR/OPS/CDER, FDA, Silver Spring, MD, 2Optical Technology Division, Physics Laboratory, NIST, Gaithersburg, MD, 3Global Biopharmaceutical Development, Sandoz, Princeton, NJ
Background: Identifying measurement process variability and optimizing measurement protocol are critical for Terahertz analysis of pharmaceuticals.
Methods: For THz spectral analysis, either tablet components (drug and excipients) or crushed theophylline tablets were mixed with polyethylene (PE) powder (~10 wt%), then compressed into THz transparent disks of thickness 2 mm in a 13 mm die at approximately 200 psi pressure. Prior to acquiring THz spectra, each disk was dried in the air-purged FTIR instrument (Nicolet Magna 550 with THz Si-coated beamsplitter and DTGS detector) for various times to remove moisture from the instrument. THz spectra were recorded at 4 cm-1 spectral resolution and 64 spectral averages. THz absorption spectra were corrected for PE matrix by ratioing against a standard pure PE pellet spectrum.
Results: Lower PE loading yields spectra of smoother baselines. Characteristic THz absorption peaks exist for crystalline materials, but not for amorphous components. When disc drying time increased from 1 min to 1hr, the wave-number shifts at 301 cm-1 are 30, 6, 50, 17, 29, and 58 cm-1for PE, theophylline, lactose, MCC, starch, and MgS, respectively; significant changes were observed for both the tablet THz measurement raw data and the tablet optical density data obtained from ratioing method.
Conclusions: Screening experiments yield optimal THz measurement process conditions: ca. 10 wt% PE loading and 1 hr disc drying time based on considerations from THz spectrum baseline shift, sample absorption, and PE scattering.