Polymorphs,Cocrystal And Quantitative Analysis Of Sartans Pharmaceutical Compounds Based On THz-TDS Technique

As a wave between the microwave and the infrared,terahertz wave,0.1THz~10 THz,has some advantages.The terahertz spectrum can detect lattice vibration,molecular vibration and so on,which can show molecule configuration and conformation.Moreover,a variety of drugs have characteristic peaks in this range.In this thesis,polymorphs,cocrystal and hyphenated drugs of sartans pharmaceutical compounds have been detected by Terahertz time domain spectroscopy(THz-TDS).The spectra show that different crystal forms have different characteristic absorption in THz range.Therefore,the spectra can be used to identify effective crystal and detect molecular structure.The density functional theory is adopted to simulate molecular structure.The work finished in this thesis is as the following:1.THz-TDS has been used to measure six sartan pharmaceutical compounds(losartan,valsartan,candesartan,irbesartan,telmisartan,olmesartan).The absorption spectra and refractive index spectra of six pharmaceutical compounds have been obtained.The absorption spectra show that six pharmaceutical compounds have disparate characteristic peaks in 0.2-2.0 THz range.The molecular structure of six pharmaceutical compounds has been analyzed combining with density functional theory calculation.2.Hydration crystal of losartan and polymorphs of irbesartan have been detected with THz-TDS.The results show that polymorphs has different characteristic peaks in the terahertz spectra.The differences of polymorphs have been explained in aspect of molecular vibration by comparing theoretical spectra and experimental spectra.3.Fumaric acid,maleic acid,benzoic acid,oxalic acid and 3.4.5-THBA have been chosen as cocrystal former to prepare cocrystal of sartan pharmaceutical compounds.The cocrystal of sartan pharmaceutical compounds has been measured by THz-TDS.The results show that cocrystals have different characteristic peaks with raw materials in the terahertz spectra.Selecting olmesartan as a model drug,thesimulation results of various olmesartan cocrystal forms have been used to estimate the molecular structure of olmesartan cocrystal.The characteristic absorption bands of cocrystal have been assigned by the simulation results of DFT calculation.4.Quantitative determination of hyphenated drugs containing valsartan and amlodipine,losartan and hydrochlorothiazide has been done.Single linear regression mode(SLR)and partial least squares mode(PLS)have been used to estimate the correlation absorption coefficient/refractive index and concentration.The partial least squares mode has better ability of quantify prediction.The correlation coefficients of the two contents with valsartan,losartan of absorption coefficient are respectively0.9943,0.9919 and the root mean squares errors of prediction are respectively0.8934% and 0.7464%.The correlation coefficients of the two contents with valsartan,losartan of refractive index are respectively 0.9943,0.9978 and the root mean squares errors of prediction are respectively 0.8654% and 0.5285%.