title: Process analytical technology (PAT): quantification approaches in terahertz spectroscopy for pharmaceutical application.
abstract: Terahertz (THz) spectroscopy and chemometric analysis of resultant absorption spectra in the 30-500 cm(-1) range has been applied to perform quantitative determination of both active ingredient and excipient concentrations of tablets. Tests were performed on a series of tablets composed of various concentrations and processes of theophylline formulated with lactose, magnesium stearate, starch or Avicel, and as a function of tablet hardness. Transmission spectra of polyethylene pellets derived from each of the samples were analyzed using three approaches. Spectral superposition method was used as an indirect measure to examine whether and when the interaction among various pharmaceutical components and the tableting history could be considered insignificant for quantification purpose. Spectral characteristic peak method was able to correlate peak maxima with correction for tablets having the same hardness. Multivariate analysis (PCR and PLS 1) was capable of correlating THz spectra with tablet concentrations. The predicted concentrations of independent samples using multivariate models agreed well with nominal concentrations. The best correlations were obtained using multivariate analysis. With these studies, the advantage of using multivariate approach was demonstrated for process analytical technology (PAT) application. Further, the feasibility of integrating THz spectroscopy and chemometrics for the purpose of quantifying pharmaceutical tablet concentrations was demonstrated.
authors.affiliation: 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, Silver Spring, Maryland 20993-0002, USA. huiquan.wu@fda.hhs.gov
authors.forename: Huiquan
authors.initials: H
authors.lastname: Wu
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Heilweil
authors.forename: Ajaz S
authors.initials: AS
authors.lastname: Hussain
authors.forename: Mansoor A
authors.initials: MA
authors.lastname: Khan
mesh_terms: D000465:Algorithms; D002138:Calibration; D005079:Excipients / Q000032:analysis*; D015999:Multivariate Analysis; D013057:Spectrum Analysis / Q000379:methods*; D013607:Tablets / Q000032:analysis*; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D005079:Excipients; D013607:Tablets