Principle and application of dsc,dta,ftir and x ray diffraction


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Principle and application of dsc,dta,ftir and x ray diffraction

  2. 2. ROLE OF THERMAL ANALYSIS IN PREFORMULATION 2 They are unique methods in the field of polymer analysis & of high value for a solid state analysis. They finds wide application in  Detection of impurity  Determination of moisture content in any drug substance or any excipient  Study of polymorphism  Characterization of hydrates & solvates  Degree of Crystallinity  Study of phase diagram  Drug excipient compatibility study  Study of complexationANAND PHARMACY COLLEGE, ANAND
  3. 3. 2)Differential Thermal analysis (DTA) 3 PRINCIPLE: A Technique in which the temperature difference between a substance and reference material is measured as a function of temperature, while the substance and reference are subjected to a controlled temperature programme. the Difference in temperature is called as Differential temp(∆t) is plotted against temp. or a function of time. Physical changes usually result in Endothermic peak ,whereas chemical reactions those of an oxidative nature are exothermic. Endothermic reaction (absorption of energy) includes vaporization, sublimation, and absorption & gives downward peak. Exothermic reaction (liberation of energy) includes oxidation, polymerization, and catalytic reaction & gives upward peak.ANAND PHARMACY COLLEGE, ANAND
  4. 4. 3) Differential scanning calorimetry 4 PRINCIPLE: It is a technique in which the energy necessary to establish a zero temp. difference between the sample & reference material is measured as a function of temp. Here, sample & reference material are heated by separate heaters in such a way that their temp are kept equal while these temp. are increased or decreased linearly. Endothermic reaction: if sample absorbs some amount of heat during phase transition then reaction is said to be endothermic. In endothermic reaction more energy needed to maintain zero temp difference between sample & reference. E.g. Melting, boiling, sublimation, vaporization, desolvation.ANAND PHARMACY COLLEGE, ANAND
  5. 5. 5 Exothermic reaction: if sample released some amount of heat during phase transition, then reaction is said to be exothermic. In exothermic reaction, less energy needed to maintain zero temp difference between sample & reference. E.g crystallization, degradation, polymerization. DSC Is widely used to measure glass transition temp & characterization of polymer. Glass Transition temp(Tg): Temp at which an amorphous polymer or an amorphous part of crystalline polymer goes from hard ,brittle state to soft,Rubbery state.ANAND PHARMACY COLLEGE, ANAND
  8. 8. Application of DTA AND DSC in pre formulation 8 Thermal analytical system can be used for detection of impurities in pharmaceutical ingredient by recording Thermogram & DTA or DSC curves. This curves could be then be compared with the curve of reference standard . Any abnormal mass changes on TG curve & irregular endotherm or exotherm peaks on DTA or DSC curve would indicate the presence of impurity.ANAND PHARMACY COLLEGE, ANAND
  9. 9.  The all thermodynamic parameter in the polymorphism substance is different like melting, sublimation temperature, kinetics, stability, solubility, heat capacity, crystal hardness & shape which are extremely important for the dosages form. During preformulation, it is important to identify the polymorph that are stable & also imp. to determine whether polymorphic transition are possible within the temp. range used for stability studies, processing (drying, milling, mixing. granulation etc.) & storage. Eg. Mannitol occurs in four forms, all melting at the same temp. & they are non hygroscopic, only form B shows a small endotherm exotherm process. ANAND PHARMACY COLLEGE, ANAND 9
  10. 10.  A sharp melting endotherm indicates the relative purity where as broad asymmetric curve suggest impurity. The presence of minute amount of substance broadens its melting range & lowers its mp. Compare to other thermal methods, DSC is best method for detection of impurity. Eg. DSC of phenacetin. ANAND PHARMACY COLLEGE, ANAND 10
  12. 12. Degree of crystallinity 12  Partial crystallinity is also a type of polymorphism.  The degree of crystallinity was determined by calorimetry.  Principle of solution calorimetry  Basis on the fact that for many solids the amorphous form is higher in energy then the crystalline form. The heat of solution of the amorphous form is expected to be more exothermic then the crystalline form.  The percentage of crystallinity (pc) may be determined in a partially crystalline sample according to the following equation. 100(∆H sample- ∆H amorphous) PC = ∆H crystal - ∆H amorphous where, sample is partially crystalline material amorphous is 100% amorphous standard & crystalline is 100% crystal standardANAND PHARMACY COLLEGE, ANAND
  13. 13. COMPATIBILITY STUDY OF DRUG WITH EXCIPIENT. 13  The early detection of Drug excipient Incompatibility is vital in pharmaceutical industry to avoid costly material wastage & time delays.  DSC with the support of x-ray diffraction & infrared spectroscopy are used as screening technique for the compatibility testing of drug with excipient.ANAND PHARMACY COLLEGE, ANAND
  14. 14. a) DSC of sparfloxacin b) DSC of pvp C) DSC of 1:1 physical mixture of Drug:pvp 14 Conclusion– incompatibility Reason: Absence of melting endotherm & exotherm isbroad.ANAND PHARMACY COLLEGE, ANAND
  15. 15. STUDY OF COMPLEXES & INCLUSION COMPOUNDS 15  The Disappearance of the DSC peak of the drug is the proof of Complexation in solid state.  Figure shows, that no complexation was obtained for a drug with ß-cyclodextrin.ANAND PHARMACY COLLEGE, ANAND
  16. 16. MINOR APPLICATIONS 16 - DSC is a valuable tool in choice of suppository base. - In study of polymer composition ,miscibility & individual characterization. - Study of tablet coating - Determinations of melting point. etc - Determination of moisture content in drug. - Checking technological quality grade of disintegrate. - Study of solid drug dispersion. - Determination of drying temp. for different excipients.ANAND PHARMACY COLLEGE, ANAND
  17. 17. GENERAL PRINCIPLE & APPLICATION OF FTIR SPECTRUM & X-RAY DIFFRACTION METHOD. 17 Generally ,this technique are not consider as thermal technique, But if used in specific condition then this technique are classified as thermal technique Fourier transform infrared spectrometers can be single beam or Double beam. Commercial FTIR spectrometers are of single beam. A double beam instrument is designed to compensate for atmosphere. In most IR spectrometer ,the optical components are manufactured in sealed & desiccated compartment with a goal of reducing water & carbon dioxide interference.ANAND PHARMACY COLLEGE, ANAND
  18. 18.  Transform multiplex devices- Fourier and Hadamard transform spectrometers. frequency-division multiplexing instruments. 18 The instruments use a single detection channal to record the optical information that has been encoded. Each individual measurement in a set of encoded data contains information about all points in the spectrum. simple IR spectra is plot of wave no  %T and called as frequency domain spectra while FTIR is time domain spectra. Fourier transform is used to convert frequency domain spectra to time domain spectra. Then time is converted to wave no. Fourier transform mathematical model is operated by computerANAND PHARMACY COLLEGE, ANAND
  19. 19. application 19Detection of impurities: -possible to determine whether given sample of compound is pure or not -by comparing the spectra of sample with reference spectra, spectrum of crude sample is blurred and not so sharp and contain many extra bands.Detection of geometrical isomerism: -trans isomer give simpler spectra than cis isomer because vibration of trans isomer give rise to little or no change in dipole moment -trans isomer shows band at lower frequency -eg. cis alkenes-970 cm-1 & trans-730-650 cm-1ANAND PHARMACY COLLEGE, ANAND
  20. 20. B) X-RAY POWDER DIFFRACTION 20 X-RAY powder Diffractometry is used to characterize spray dried & crystalline material & the binary mixtures. PRINCIPLE: x-ray are Diffracted & order of this diffraction is measured in form of graph. Diffraction occurs as a result of the interaction of radiation with electron of atom. Why only x-ray are used? Because x-rays have wavelengths of about the same magnitude as the distance between the atoms or molecules of crystal.ANAND PHARMACY COLLEGE, ANAND
  21. 21. 21  X-ray Diffraction Methods  X-ray diffraction methods are generally used for investigating the internal structures. However, the following methods are used:  (1) Laue photographic method  (2) Bragg X-ray spectrometer method  (3) Rotating crystal method  (4) Power methodANAND PHARMACY COLLEGE, ANAND
  22. 22. 22 Application of X-ray diffraction 1. Structure of Crystals The analytical applications of X-ray diffraction are numerous. The method is nondestructive and gives information on the molecular structure of the sample. Perhaps its most important use has been no measure the size of crystal planes. The patterns obtained are characteristic of the particulars compounds from which the crystal was formed. 2. Polymer Characterisation Powder method can be used to determine the degree of crystalline of the polymer. The non-crystalline portion simply scatters the X-ray beam to give a continuous background, while the crystalline portion causes diffraction lines that are not continuous.ANAND PHARMACY COLLEGE, ANAND
  23. 23. 23 Identification Of Impurity:  X-ray diffraction pattern of any specimens match with standard Presence of Additional lines on the photograph of specimen, indicate the presence of impurity. e.g In cosmetic talc, the contaminant tremolite (a potentially carcinogen ) can be detected by x-ray diffraction technique. Characterize spray dried & crystalline material. For particle size analysis.ANAND PHARMACY COLLEGE, ANAND
  24. 24. 24 XRD is the technique of choice to identify different polymorphic forms of a compound. It can also be used to identify the solvated and unsolvated (anhydrous) forms of a compound, provided their lattice structures are different. The technique can also reveal differences in the crystallinity of compounds. The XRD pattern of an amorphous (noncrystalline) compound will consist of one or more broad diffuse halosANAND PHARMACY COLLEGE, ANAND
  25. 25. (A) XRD patterns of (a) crystalline and (b) amorphous sucroseANAND PHARMACY COLLEGE, ANAND 25
  26. 26. Degree of crystallinity 26 XRD is widely used to determine the degree of crystallinity of pharmaceuticals. The procedure developed by Hermans and Weidinger is based on three assumptions. First, it must be possible to demarcate and measure the crystalline intensity (Ic) and amorphous intensity (Ia) from the powder pattern. Usually, the integrated line intensity (area under the curve), rather than the peak intensity (peak height), is measured. Second, there is a proportionality between theexperimentally measured crystalline intensity and thecrystalline fraction (xc) in the sample. Finally, a proportionalityexists between the experimentally measuredamorphous intensity and the amorphousfraction (xa) in the sample. The degree of crystallinity is given below.ANAND PHARMACY COLLEGE, ANAND
  27. 27. 27X=Ic +100 Ic + qIa/p where p and q are proportionality constants. Thevalues of Ia and Ic can be determined for samples ofvarying degrees of crystallinity. A plot of the measuredvalues of Ia against those of Ic will result in a straightline, and the intercepts on the y- and x-axes will providethe intensity values of the 100% amorphous and100% crystalline materials, respectively. This methodwas used by Nakai et al.[17] to estimate the degree ofcrystallinity of lactose that had been milled for varioustime periods (Fig. 8). If the value of (q/p) is known, thedegree of crystallinity of an unknown sample can becalculated from the experimentally determined valuesof Ic and Ia.ANAND PHARMACY COLLEGE, ANAND
  28. 28. 28 Fig. 8 A plot of the integrated amorphous intensity (Iam) as a function of the integrated crystalline intensity (Ic) for lactose samples milled for various time periods.ANAND PHARMACY COLLEGE, ANAND