Dsc: interpretaion and application
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Transcript of Dsc: interpretaion and application
DSC: PRINCIPLE, APPLICTION AND INTERPRETATIONP R E S E N T E D B Y: R A H U L K U M A R
M . P H A R M A
B I T S P I L A N I
R A J A S T H A N
CONTENTSIntroduction
Types/ Modifications
Application
Sample Preparation
Calibration
Interpretation
References
INTRODUCTIONThermal 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
TYPES OF TAHRMAL ANALYSISIt includes – DTA, DSC
DSC is further categorized as :
Power-compensated DSC
Heat flux DSC
a)DTA b) PC DSC c) HF DSC
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
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
For accurate quantitative work the thermal mass of the sample and reference pans
should be matched.
Sample sizes of 3–5 mg, sometimes with less than 1 mg optimum result may be obtain
CalibrationTo ensure expected working condition and accurate results.
Calibration AccessoriesMicron Balance
Crucible sealing press
Crucible (2) : sample and reference 40 microliter
Calibration toolbox
Calibration material
Calibration Process
Calibration standards have classically been metals such as indium, tin, bismuth and
lead.
Separate calibration is required at each scan rate used
Interpretation: Exothermic Transition -Up
Endothermic Transition -DownDifferential scanning calorimetry scan of sucrose (undried), showing the glass transition temperature, (Tg), recrystallization exothermtemperature (Tc) and enthalpy (DHc), melting endotherm temperature (Tm) and enthalpy (DHf) and onset of degradation 10K /min. Endothermic transitions are down
Melting PointWhere To is onset temperature of melting, Te is the extrapolated onset melting temperature,enthalpy of fusion (⌂Ho), Tm is peak melting temperature
Purity
Ts = Te – RTe 2X
ΔHoF
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,
ΔHo is the enthalpy of fusion of the pure compound (J/mol) and
F is the fraction of the sample molten at Ts.
Polymorphism
CRYSTALLINE OR AMORPHOUS COMPOUND ?
Regulatory issuesThe 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.
REFERENCES1. 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
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