Dsc: interpretaion and application

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1. DSC: PRINCIPLE, APPLICTION AND INTERPRETATION PRESENTED BY: RAHUL KUMAR M. PHARMA BITS PILANI RAJASTHAN

2. CONTENTS Introduction Types/ Modifications Application Sample Preparation Calibration Interpretation References

3. INTRODUCTION Thermal analytical methods have become important tools for the development of modern medicines . These instruments provide quantitative information about exothermic, endothermic and heat capacity changes as a function of temperature and time (such as melting, purity and glass transition temperature). Differential scanning calorimetry instruments are primarily used in the earliest stages of drug development , where experiments are often of an exploratory nature

4. TYPES OF TAHRMAL ANALYSIS It includes – DTA, DSC DSC is further categorized as : Power-compensated DSC Heat flux DSC

5. a)DTA b) PC DSC c) HF DSC

6. Application Glass transitions Melting and boiling points Crystallization time and temperature Percent crystallinity Heats of fusion and reactions Specific heat capacity Oxidative/thermal stability Rate and degree of cure Reaction kinetics Purity

7. Sample Preparation DSC samples are analyzed in small metal pans, designed for optimal thermal conductivity and minimum reaction with the samples (for example, aluminium alloy , platinum, stainless steel and silver ). Pans may be open, pin-hole, covered or sealed

8. For accurate quantitative work the thermal mass of the sample and reference pans should be matched . S ample sizes of 3–5 mg, sometimes with less than 1 mg optimum result may be obtain

9. Calibration To ensure expected working condition and accurate results.

10. Calibration Accessories Micron Balance Crucible sealing press Crucible (2) : sample and reference 40 microliter Calibration toolbox Calibration material

11. Calibration Process

12. Calibration standards have classically been metals such as indium, tin, bismuth and lead . Separate calibration is required at each scan rate used

13. Interpretation: Exothermic Transition -Up

14. Endothermic Transition -Down Differential scanning calorimetry scan of sucrose (undried ), showing the glass transition temperature, ( Tg ), recrystallization exotherm temperature (Tc) and enthalpy ( DHc ), melting endotherm temperature (Tm) and enthalpy ( DHf ) and onset of degradation 10K /min. Endothermic transitions are down

15. Melting Point Where To is onset temperature of melting, Te is the extrapolated onset melting temperature, enthalpy of fusion (⌂Ho), Tm is peak melting temperature

16. Purity Ts = Te – R T e 2X Δ HoF Van’t Hoff eq. A streight line relationship is expected between Ts and 1/F for pure compound. where Ts is the sample temperature at equilibrium (K ), Te is the melting temperature of the pure component (K ), R is the gas constant (8.314 J/ mol /K), X is the molar fraction of the impurity , Δ Ho is the enthalpy of fusion of the pure compound (J/ mol ) and F is the fraction of the sample molten at Ts.

17. Polymorphism

18. CRYSTALLINE OR AMORPHOUS COMPOUND ?

19. Regulatory issues The use of DSC for the determination of transition temperatures and sample purity is described in the United States Pharmacopeia . It is stated that detailed records should be kept of all experimental parameters, and that special attention be given to the number of significant figures reported in the results. The patent or regulatory status of newly discovered drug forms may depend on the quality of the DSC maintenance and calibration records.

20. REFERENCES 1. Barnes , A.F., Hardy, M.J. and Lever,T.J. (1993) J.Therm.Anal. 40, 499–509 2. Ford, J.L. and Timmins, P. (1989) Pharmaceutical Thermal Analysis:Techniques and Applications , Halsted Press, New York, NY, USA 3. Burroughs, P. (1980) Anal. Proc. (London) 17, 231–234 4. Richardson, M.J. (1997) Thermochim.Acta 300, 15–28 5. Turi , E.A., ed. (1997) Thermal Characterization of Polymeric Materials (2nd edn ), Academic Press, San Diego, CA, USA 6. Jones, K.J. et al. (1997) Thermochim.Acta 304/305, 187–199 7. Schawe , J.E.K. (1996) Thermochim.Acta 271, 127–140 8. Boller, A., Jin,Y. and Wunderlich, B. (1994) J.Therm.Anal . 42, 307–330

21. 9. Wunderlich, B. et al. (1998) Thermochim.Acta 324, 77–85 10. Craig, D.Q.M. and Royall, P.G. (1998) Pharm. Res. 15, 1152–1153 11. Hensel, A. and Schick, C. (1997) Thermochim.Acta 304/305, 229–237 12. Varma-Nair, M. and Wunderlich, B. (1996) J.Therm.Anal. 46, 879–892 13. Barker, A.D. (1993) J.Therm.Anal . 40, 799–805 14. Price, D.M. (1995) J.Therm.Anal. 45, 1285–1296 15. Tan, Z-C. and Sabbah, R. (1994) J.Therm.Anal . 41, 1577–1592