This study is supported by Tubitak.

1. METHOD DEVELOPMENT FOR ACTIVE PHARMACEUTICAL INGREDIENT ANALYSIS IN TERAHERTZ REGION Laser Spectroscopy MERVE DOĞANGÜN, ENİS ARIK, OKAN ESENTÜRK Chemistry Department, Middle East Technical University, 06800 Çankaya, Ankara e171884@metu.edu.tr; eokan@metu.edu.tr Group • Working range: 30-700 cm-1 • Source: ETC • Beam Splitter: DTGS-PE • Working range: 5-150 cm-1 • THz Generation and • Detection Crystal: ZnTe, 1mm Abstract: Effective control of the pharmaceutical tablets is of great importance. This study that is based on terahertz spectroscopy aims to develop a fast, active, and non-destructive material characterization method. TerahertzSpectroscopy allow a structural analysis in a wide scan range of 5 to 700 cm-1. In this study, active pharmaceutical ingredients that are used in commercial drugs are characterized using fingerprint spectra in 30-700 cm-1 range by THz-FTIR Spectroscopy. http://www.shutterstock.com/pic-2845058/ Microwaves Terahertz Infrared APPLICATIONS INTRODUCTION The THz-waves provide important information about the low-frequency vibrational modes including hydrogen bonding, rotational modes of gases and crystal phonon modes.1 109 1010 1011 1012 1013 1014 Terahertz absorption images (commercial and test tablets)4 Tablet surface ingredient distribution (near-IR imaging)1 Intensity Absorbance Delay Stage • BIOTECHNOLOGY2 • Determination of high order protein structures • Genetic sensing • Biomedical Imaging • PHARMACEUTICS 2 • Characterisation of tablet coating & polymorphism • Inspection of tablet core Integrity • SECURITY3 • Illicit Drug & Explosive Detection • Inspection of biological and chemical agents 1 THz = 1ps, 300 μm, 33 cm-1 , 4.1 meV, 47.6 K Beam Splitter BB Source → low energy waves → non-destructive → penetrate into the material → transmit through nonpolar molecules (plastic, ceramics) SAMPLE Detector • EXPERIMENTAL • Active pharmaceutical powders are ground in an agate mortar without further purification • Specified amount of the particles is mixed with high density polyetylene and compressed into a 1.3 cm diameter pellet with a pressure of 2 tons for 5 minutes. • Prepared pellets are directly placed in the sample compartment of the THz-FTIR instrument. RESULTS AND DISCUSSION MEASUREMENT OF MATRIX MATERIALS Hz Raw Spectra Absorbance Spectra Thermo Scientific Nicolet 6700 FTIR Spektrometer MEASUREMENT OF ACTIVE PHARMACEUTICALS 1. Benzydamine 2. Ibuprofen Wollaston Prism Cubic Mirror • HDPE transmission in Far-IR region is very high due to its nonpolar characteristic. • Therefore, HDPE forms a good matrix to disperse the active material. Terahertz Detection Crystal Parabolic Mirror Ti:Sapphire Laser Beam Combiner SAMPLE Terahertz Generation Crystal 3. Naproxen Terahertz Time Domain Spectrometer (THz-TDS) For easier comparison, the spectra are offset by one absorbance unit. Broadband Dielectric Mirror Beam Splitter • References • Ajito, K.; Ueno Y.; Song H., NTT Technical Review, 2012 ,10(2) • Taday, P. F., Phil. Trans. R. Soc. London, 2004, 362, 351-364 • CONCLUSION • Strong absorption peaks are observed in THz region. • THz waves can be used as a tool to characterize active pharmaceuticals. • There are sufficient differences between the three active pharmaceuticals to make it possible to use for identification. • FUTURE DIRECTIONS • Measurement of samples with THz-TDS • Assay of active pharmaceuticals in tablets • Investigation of tablet homogeneity Central λ: 800nm This study is supported by Tubitak. • 3. Kemp, M. C.; Taday, P. F.; Cole, B. E.; Cluff J. A.; Fitzgerald, A. J.; Tribe, W. R., Proc of SPIE, 2003, 5070, 8 • 4. Application of imaging analysis technology http://www.ds-pharma.com/rd/drug_discovery/product.html