Investigation In Properties Of Pharmaceutical Polymorphs Based On Terahertz Spectroscopical Technique

Terahertz (THz) wave is generally defined as the frequency whitin0.1~10THz range, between the microwave and infrared in the electro spectrum.The twisting or wagging vibrational modes and intermolecular interaction of mostmolecules will show resonance absorption in this specific terahertz region. Manyunique absorption peaks of drugs will be observed in their THz absorption spectra, sothat different drugs can be identified by THz technique. In this thesis, time-domainspectroscopy (THz-TDS) is used to investigate the vibrational modes of isomers andpolymorphs of different drugs, combined with Raman and Fourier transform infrared(FT-IR) spectroscopical techniques. We also use THz-TDS to determinate cocrystalformation and crystal transformation of pharmaceutical polymorphs.In this thesis, all we have done are as follows:(1)Two kinds of THBA’s isomers (3,4,5-THBA and2,4,6-THBA) were chosen tobe studied by THz-TDS. The fingerprint peaks of these two isomers were found intheir THz absorption spectra. The result proves that it can be used to determineisomers drugs with THz-TDS technique.(2)The anhydrous and hydrated3,4,5-THBA’s pharmaceutical polymorphs wereinvestigated by FT-IR, Raman and THz spectroscopical techniques. Different parts ofvibrational modes were observed in the FT-IR and Raman spectra. And absorptionalfingerprint peaks of these polymorphs were also found in THz absorption spectra.They were significantly different, so that these techniques can be used to identifythese pharmaceutical polymorphs. The theoretical simulation of single-molecule byGaussian03software is used to assign the different vibrational modes of hydrated andanhydrous3,4,5-THBA polymorphs. These results can help us deeply understandboth intramoleuclar and intermolecular interactions between different pharmaceuticalpolymorphs, and also provide fundmental work in detecting them with spectroscopical techniques.(3)THz-TDS was used to determinate crystal transformation between hydratedand anhydrous3,4,5-THBA’s polymorphs. Less significant change can be observedin their absorption spectra of the frequency range below1.4THz. But significantchange was found higher than this range. The fingerprint peaks shifted, or evendisappeared, and some new peaks were observed in the spectrum of another crystal.The results explained that the crystal transformation can be monitored by THz-TDS.(4)Cocrystal formation between piracetam and2,5-DHBA using grinding methodhas been characterized by THz spectroscopical techniques, and the results indicatethat the THz-TDS can be used to determine whether the pharmaceutical cocrystal isproduced or not. THz-TDS was also used to monitor the formation process ofcocrystal between piracetam and2,5-DHBA with different grinding time. The resultsshow that THz-TDS method can be used to real-time monitor pharmaceuticalcocrystal formation. Such study provides us important experimental benchmark indirectly quantitative analysis of similar cocrystal formations in pharmaceutical fields.