This study is supported by Tubitak

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. Terahertz Spectroscopy 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.

This study is supported by Tubitak.

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.

References

1. Ajito, K.; Ueno Y.; Song H., NTT Technical Review, 2012 ,10(2) 2. Taday, P. F., Phil. Trans. R. Soc. London, 2004, 362, 351-364

RESULTS AND DISCUSSION

Terahertz Time DomainSpectrometer (THz-TDS)

Terahertz Generation

Crystal

SAMPLE

Wollaston Prism

Ti:Sapphire Laser

Broadband Dielectric Mirror Beam

Splitter

Beam Combiner

Cubic Mirror

Parabolic Mirror

Terahertz Detection Crystal

Working range: 5-150 cm-1

THz Generation and Detection Crystal: ZnTe, 1mm

MEASUREMENT OF MATRIX MATERIALS

700 600 500 400 300 200 1000,0

0,2

0,4

0,6

0,8

Abso

rban

ce

Wavenumber (cm-1)

5 mg Benzydamine in 50 mg HDPE

186.10

83.89

700 600 500 400 300 200 1000,0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

50 mg pure Ibuprofen

5 mg Ibuprofen in 50 mg HDPE

Abso

rban

ce

Wavenumber (cm-1)

114.75217.92269.02

334.11

0

1

2

3

4

5

6

MEASUREMENT OF ACTIVE PHARMACEUTICALS

Terahertz absorption images(commercial and test tablets)4

Tablet surface ingredient distribution (near-IR imaging)1

Infrared

1014101310121011

Microwaves Terahertz

1010109

Hz

→ low energy waves → non-destructive → penetrate into the material→ transmit through nonpolar molecules (plastic, ceramics)

1 THz = 1ps, 300 μm, 33 cm-1 , 4.1 meV, 47.6 K

600 300 00

20

40

60

Ampli

tude

Wavenumber (cm-1)

HDPE(Sigma A)_50mg HDPE (Sigma A)_100mg HDPE (Petkim)_100mg Wheat Starch_20mg

Absorbance Spectra

300 250 200 150 100 500

1

2

3

Abso

rban

ce

Wavenumber (cm-1)

Wheat Starch_20 mg HDPE (Petkim)_100mg HDPE (SA)_50mg HDPE (SA)_100mg

Raw Spectra

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.

For easier comparison, the spectra are offset by one absorbance unit.

700 600 500 400 300 200 100-1,0

-0,5

0,0

0,5

1,0

1,5

2,0

Abso

rban

ce

Wavenumber (cm-1)

Naproxen Benzydamine Ibuprofen

1. Benzydamine 2. Ibuprofen

3. Naproxen

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

MERVE DOĞANGÜN, ENİS ARIK, OKAN ESENTÜRKChemistry Department, Middle East Technical University, 06800 Çankaya, Ankara

e171884@metu.edu.tr; eokan@metu.edu.tr

Laser Spectroscopy

Group

METHOD DEVELOPMENT FOR ACTIVE PHARMACEUTICAL INGREDIENT ANALYSIS IN TERAHERTZ REGION

http://www.shutterstock.com/pic-2845058/

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

Intensity Absorbance

APPLICATIONS

BIOTECHNOLOGY 2

•Determination of high order protein structures•Genetic sensing•Biomedical Imaging

PHARMACEUTICS 2

•Characterisation of tablet coating & polymorphism•Inspection of tablet core Integrity

SECURITY 3

•Illicit Drug & Explosive Detection•Inspection of biological and chemical agents

BB Source

Beam Splitter

Delay Stage

SAMPLE

Detector

Working range: 30-700 cm-1

Source: ETCBeam Splitter: DTGS-PE

Thermo Scientific Nicolet 6700 FTIR Spektrometer

Central λ: 800nm

700 600 500 400 300 200 1000,0

0,2

0,4

0,6

0,8 5 mg Naproxen in 50 mg HDPE

Abso

rban

ce

Wavenumber (cm-1)

214.54

0,0

0,5

1,0

1,5

2,0

2,5

3,0

3,5

50 mg pure Naproxen

3. Kemp, M. C.; Taday, P. F.; Cole, B. E.; Cluff J. A.; Fitzgerald, A. J.; Tribe, W. R., Proc of SPIE, 2003, 5070, 84. Application of imaging analysis technology http://www.ds-pharma.com/rd/drug_discovery/product.html