Process analytical technology (PAT): effects of instrumental and compositional variables on terahertz spectral data quality to characterize pharmaceutical materials and tablets.
The aim of this study was to use terahertz spectroscopy to characterize pharmaceutical materials and tablets, and to understand the effects of measuring conditions and compositional variability on the data quality. Tests were performed on five formulation components (theophylline, lactose, starch, Avicel, magnesium stearate) and a series of tablets composed of various concentrations of theophylline and excipients. Transmission spectra of polyethylene (PE) disks derived from each of the samples were analyzed. Three factors (component loading, component chemistry, and disk drying time) were screened as critical factors associated with the magnitude and location of THz absorbance peaks. Applying the standard sample spectra divided by PE reference spectra ratio method revealed that, to a large extent, PE was responsible for the disk drying time dependence. Direct spectral feature analysis along with mass-transfer analysis of the disk drying process revealed THz absorption peak maxima of lactose (255 cm(-1)) and water (54 and 210 cm(-1)) which is also supported by literature values for the peak maxima assignment for water. Particle scattering due to specimen and PE was found to be also partially responsible for the observed spectral intensities. The importance of THz spectroscopy was demonstrated for characterization of pharmaceutical materials and tablet.
Wu
Huiquan
H
Division of Product Quality Research (DPQR, HFD-940), Office of Testing and Research, Office of Pharmaceutical Science, Center for Drug Evaluation and Research, Food and Drug Administration, MD 20993, USA. huiquan.wu@fda.hhs.gov
Heilweil
Edwin J
EJ
Hussain
Ajaz S
AS
Khan
Mansoor A
MA
D002482:Cellulose / Q000737:chemistry; D005079:Excipients / Q000737:chemistry; D007785:Lactose / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry; D013057:Spectrum Analysis / Q000379:methods*; D013213:Starch / Q000737:chemistry; D013229:Stearic Acids / Q000737:chemistry; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods*; D013806:Theophylline / Q000737:chemistry
D005079:Excipients; D004364:Pharmaceutical Preparations; D013229:Stearic Acids; D013607:Tablets; C031183:stearic acid; D002482:Cellulose; D013213:Starch; D013806:Theophylline; D007785:Lactose; C109691:microcrystalline cellulose