Application of Terahertz spectroscopy in pharmaceutical industry
1. TERAHERTZ
SPECTROSCOPY
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Presented by:
Medtiya Pravin Pokarlal
Reg.no. PE/2019/314
GE -511
Department of Pharmaceutics
National Institute of Pharmaceutical Education and Research, Hyderabad
Department of Pharmaceuticals, Ministry of Chemicals & Fertilizers, Govt. of India.
3. INTRODUCTION
12-Jun-20 Baxter et al., Analytical chemistry, 2011, 83, 4342–4368 3
• Terahertz(THz) – unit of electromagnetic wave frequency to trillion
hertz
• Absorption spectroscopy for identifying molecular species
• Probe physical phenomena such as low-energy excitations and carrier
dynamics in electronic materials
Parameter Near IR Mid IR Terahertz Far IR Microwave
Frequency (Thz) 384 -119 119 - 6 20 - 0.1 6 - 0.29 0.3 – 0.0003
Wavelength(µm) 0.78 - 2.5 2.5 - 50 15 - 3000 50 - 1000 1000 – 1*106
Wavenumber(cm-1) 12800 - 4000 4000 - 200 666 – 3.33 200 - 10 10 – 0.01
Properties :
Water
absorption
Non
ionising
Penetrable
4. PRINCIPLE
• Coherent detection is used , so the amplitude and phase of the THz pulse are measured, which
allows the absorption coefficient as well as refractive index spectra to be determined
12-Jun-20 Baxter et al., Analytical chemistry, 2011, 83, 4342–4368
4
THz – Terahertz
5. A. Beam splitter
B. Emitter
C. Parabolic mirror
D. Detector
E. Delay stage
F. Sample
INSTRUMENTATION
12-Jun-20 Baxter et al., Analytical chemistry, 2011, 83, 4342–4368
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Femtosecond laser
computer
A
B C
E
D
F
6. ADVANTAGES
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Taday et al., Journal of pharmaceutical sciences, 2003, 92, (4), 831-838 6
• Imaging enables direct measurement of
sample thickness, refractive index and
absorption coefficient
Near infrared
• No phase change or photochemical
change occurs
• It measures surface as well as inside
Raman
spectroscopy
• Dynamic range is high as compared to
FTIR
Fourier
transform
infrared(FTIR)
9. CASE STUDY NO. 1
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Conclusion
• Peak frequency of DL-alanine is different from those of L- and D-
alanine
• These indicate that the absorption bands in the THz range are sensitive
to the crystal structures of amino acids
85.7 cm-
174.4 cm-
1
41.5 cm-1
10. CASE STUDY NO. 2
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• 18 batch tablet prepared & measured the effective refractive index(ηeff) and
absorption coefficient(α) of 6 tablets per batch
• The magnitude of ηeff represents the optical density of the sample and thus it
reflects both changes in tablet porosity as well as granule density,
• ηeff linearly correlates with disintegration time
11. CASE STUDY NO. 2
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Conclusion
• ηeff provide promising predictors for the disintegration time of tablets
• Nondestructively prediction of critical quality attributes of tablets
12. CASE STUDY NO. 3
• They explored the vibrational properties of co-amorphous drugs in
molecular level with Raman and THz spectroscopy
• Detection of crystalline and amorphous drugs could be better
distinguished than Raman spectroscopy
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13. CASE STUDY NO. 3
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NAP - naproxen
IND – indomethacin
CIM - cimetidine
14. CASE STUDY NO. 3
Conclusion
• THz spectra could distinguish the crystalline and amorphous drugs more clearly than the Raman
spectra
• The stability of co-amorphous drugs was better than their neat amorphous
• The intermolecular interactions played a crucial role in the transformation of the co-amorphous
drugs into the crystalline ones
• In conclusion, multispectral detection on co-amorphous systems proposed some supplement of the
molecular interaction mechanism and provided a direction for the choice of components to improve
the stability of amorphous form
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15. CONCLUSION & FUTURE ASPECT
• It has enabled identification of polymorphs and their quantification, tablet coatings in
pharmaceutical applications, and it has provided new imaging modalities for biomedicine
• Terahertz enabled to evaluate tablet non-destructively in in-line manufacturing line, thereby
reducing time & money for industries
• High throughput screening will be available for drug development in near future
• By improving advancements in this technology we can diagnose diseases like cancer
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16. BIBLIOGRAPHY
1. Baxter JB, Guglietta GW. Terahertz spectroscopy. Analytical chemistry. 2011 May 2;83(12):4342-68.
2. Taday PF. Applications of terahertz spectroscopy to pharmaceutical sciences. Philosophical Transactions
of the Royal Society of London. Series A: Mathematical, Physical and Engineering Sciences. 2003 Dec
19;362(1815):351-64.
3. Yamaguchi M, Miyamaru F, Yamamoto K, Tani M, Hangyo M. Terahertz absorption spectra of L-, D-, and
DL-alanine and their application to determination of enantiometric composition. Applied Physics
Letters. 2005 Jan 31;86(5):053903.
4. Markl D, Sauerwein J, Goodwin DJ, van den Ban S, Zeitler JA. Non-destructive determination of
disintegration time and dissolution in immediate release tablets by terahertz transmission
measurements. Pharmaceutical research. 2017 May 1;34(5):1012-22.
5. Liu W, Liu Y, Huang J, Lin Z, Pan X, Zeng X, de la Chapelle ML, Zhang Y, Fu W. Identification and
investigation of the vibrational properties of crystalline and co-amorphous drugs with Raman and
terahertz spectroscopy. Biomedical optics express. 2019 Aug 1;10(8):4290-304.
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