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

Principle and application of
DSC,DTA,FTIR and X-ray
diffraction
1

GUIDED BY:. VAISHALI THAKKAR
PREPARED BY:KARTIK DUDHAT
ANAND PHARMACY COLLEGE

ANAND PHARMACY COLLEGE, ANAND

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 complexation


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.


3) Differential scanning calorimetry
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 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.



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 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 6

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.


 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.


 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.



Degree of crystallinity

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 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



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.


a) DSC of sparfloxacin
b) DSC of pvp
C) DSC of 1:1 physical mixture of Drug:pvp
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Conclusion– incompatibility
Reason: Absence of melting endotherm & exotherm
isbroad.


STUDY OF COMPLEXES &
INCLUSION COMPOUNDS
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 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.


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.


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.


 Transform multiplex devices- Fourier and Hadamard
transform spectrometers.
 frequency-division multiplexing instruments.
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 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
computer


application
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Detection 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-1

B) X-RAY POWDER DIFFRACTION
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 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.


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 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 method


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.


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 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.


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 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
halos


(A) XRD patterns of (a) crystalline and
(b) amorphous sucrose


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 the
experimentally measured crystalline intensity and the
crystalline fraction (xc) in the sample. Finally, a proportionality
exists between the experimentally measured
amorphous intensity and the amorphous
fraction (xa) in the sample. The degree of crystallinity is given below.

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X=Ic +100
Ic + qIa/p
 where p and q are proportionality constants. The
values of Ia and Ic can be determined for samples of
varying degrees of crystallinity. A plot of the measured
values of Ia against those of Ic will result in a straight
line, and the intercepts on the y- and x-axes will provide
the intensity values of the 100% amorphous and
100% crystalline materials, respectively. This method
was used by Nakai et al.[17] to estimate the degree of
crystallinity of lactose that had been milled for various
time periods (Fig. 8). If the value of (q/p) is known, the
degree of crystallinity of an unknown sample can be
calculated from the experimentally determined values
of Ic and Ia.


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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.


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Thank you


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

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