Abstract
In pharmaceuticals, pseudo-polymorphism, e.g., the existence of hydrate and anhydrous forms, affects their physicochemical characteristics. Therefore, the evaluation of pseudo-polymorphism is one of the most important quality analyses. In this research, we investigate the real-time monitoring of the hydration reaction of theophylline using terahertz attenuated total reflection time domain spectroscopy (THz-attenuated total reflection (ATR)-TDS). We continuously measured a mixture of hydroxypropyl cellulose solution and theophylline anhydrous (TPA) while keeping it pressed to the ATR surface. We observed that the absorption peaks derived from TPA decreased and those derived from theophylline monohydrate (TPM) increased with time, demonstrating that the hydrate reaction of TPA can be monitored. Subsequently, we performed an accurate and quantitative evaluation of the hydration reaction by calculating the temporal changes in the crystal form ratio of TPM based on the changes in its second derivative peak intensity followed by a curve fitting. In addition, we performed real-time monitoring of the reaction using two different pressure mechanisms, finding that using a weight to apply pressure provided better reproducibility than using a screw. This study demonstrates that THz spectroscopy is a useful method for the evaluation of pseudo-polymorphism in pharmaceuticals.
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Data Availability
Data sets generated and analyzed during the current study are available from the corresponding author on reasonable request.
References
T. Sakamoto, T. Sasaki, N. Katori, Y. Goda, J. Infrared Milli Terahz Waves 37, 1007 (2016) https://doi.org/10.1007/s10762-016-0288-3
M. Ono, Y. Tozuka, T. Oguchi, K. Yamamoto, Chem. Pharm. Bull. (Tokyo) 49, 1526 (2001) https://doi.org/10.1248/cpb.49.1526
M. Otsuka, Y. Kanai, Y. Hattori, J. Pharm. Sci. 103, 2924 (2014) https://doi.org/10.1002/jps.24006
H.-B. Liu, Y. Chen, X.C. Zhang, J. Pharm. Sci. 96, 927 (2007) https://doi.org/10.1002/jps.20782
S. Sakai, D. Yang, T. Yasuda, K. Akiyama, T. Kuga, A. Kano, F. Shiraishi, S. Amekawa, S. Ohtsuka, K. Nakaguchi, S. Yamaguchi, ACS Omega 4, 2702 (2019) https://doi.org/10.1021/acsomega.8b03311
J.A. Zeitler, K. Kogermann, J. Rantanen, T. Rades, P.F. Taday, M. Pepper, J. Aaltonen, C.J. Strachan, Int. J. Pharm. 334, 78 (2007) https://doi.org/10.1016/j.ijpharm.2006.10.027
E.M. Paiva, Q. Li, A.J. Zaczek, C.F. Pereira, J.J.R. Rohwedder, J.A. Zeitler, Mol. Pharm. 18, 3578 (2021) https://doi.org/10.1021/acs.molpharmaceut.1c00476
J. Hisazumi, T. Suzuki, N. Wakiyama, H. Nakagami, K. Terada, Chem. Pharm. Bull. (Tokyo) 60, 831 (2012) https://doi.org/10.1248/cpb.c11-00007
M. Mohara, M.P. Davis, T.M. Korter, K. Shimura, T. Ono, K. Aiko, J. Phys. Chem. A 126, 2879 (2022) https://doi.org/10.1021/acs.jpca.2c00301
H. Hirori, K. Yamashita, M. Nagai, K. Tanaka, Jpn. J. Appl. Phys. 43, L1287 (2004) https://doi.org/10.1143/JJAP.43.L1287
S. Kawabe, M. Seki, H. Tabata, Appl. Phys. Lett. 108, 081103 (2016) https://doi.org/10.1063/1.4942411
K. Shiraga, Y. Ogawa, N. Kondo, A. Irisawa, M. Imamura, Food Chem. 140, 315 (2013) https://doi.org/10.1016/j.foodchem.2013.02.066
G. Takebe, Y. Kawada, K. Akiyama, H. Takahashi, H. Takamoto, M. Hiramatsu, J. Pharm. Sci. 102, 4065 (2013) https://doi.org/10.1002/jps.23716
A. Nakanishi, Y. Kawada, T. Yasuda, K. Akiyama, H. Takahashi, Rev. Sci. Instrum. 83, 033103 (2012) https://doi.org/10.1063/1.3692743
K. Akiyama, K. Horita, T. Sakamoto, H. Satozono, H. Takahashi, Y. Goda, J. Infrared Milli. Terahz Waves 40, 1160 (2019) https://doi.org/10.1007/s10762-019-00642-9
K. Horita, K. Akiyama, T. Sakamoto, K. Takahashi, H. Satozono, J. Infrared Milli. Terahz Waves 42, 1094 (2021) https://doi.org/10.1007/s10762-021-00833-3
D.A. Newnham, P.F. Taday, Appl. Spectrosc. 62, 394 (2008) https://doi.org/10.1366/000370208784046731
P.C. Upadhya, K.L. Nguyen, Y.C. Shen, J. Obradovic, K. Fukushige, R. Griffiths, L.F. Gladden, A.G. Davies, E.H. Linfield, Spectrosc. Lett. 39, 215 (2006) https://doi.org/10.1080/00387010600636916
A. Menon, S. Bhandarkar, Int. J. Pharm. 286, 125 (2004) https://doi.org/10.1016/j.ijpharm.2004.07.028
H. Wikström, P. J. Marsac, L. S. Taylor, J. Pharm. Sci. 94, 209 (2005) https://doi.org/10.1002/jps.20241
Acknowledgements
We thank A. Hiruma, T. Maruno, and H. Toyoda for their encouragement. We also thank T. Yasuda for technical support.
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This research was supported by the AMED under grant number JP23ak0101189.
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All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Kazuhiro Takahashi. The first draft of the manuscript was written by Kazuhiro Takahashi, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Takahashi, K., Akiyama, K., Horita, K. et al. Real-time Monitoring of Hydration Reaction of Theophylline Anhydrous via Terahertz Attenuated Total Reflection Time Domain Spectroscopy. J Infrared Milli Terahz Waves 45, 444–453 (2024). https://doi.org/10.1007/s10762-024-00986-x
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DOI: https://doi.org/10.1007/s10762-024-00986-x