Modern Pharmaceutics class

1. DRUG EXCIPIENT INTERACTION:
DIFFERENT METHOD ANALYSIS
Presented by
(Dr) Kahnu Charan Panigrahi
Asst. Professor, Research Scholar,
Roland Institute of Pharmaceutical Sciences,
(Affiliated to BPUT)
Web of Science Researcher ID: AAK-3095-2020
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2. CONTENTS
• THERMOGRAVIMETRIC ANALYSIS(TGA)
• DIFFERENTIAL THERMAL ANALYSIS (DTA)
• DIFFERENTIAL SCANNING CALORIMETRY (DSC)
• X-RAY POWDER DIFFRACTION (XRD)
• FT-IR SPECTROSCOPY
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3. Thermogravimetric analysis(TGA)
• Thermogravimetric analysis (TGA) is a method of thermal
analysis in which the mass of a sample is measured over time
as the temperature changes.
• This measurement provides information about physical
phenomena, such as phase transitions, absorption and
desorption as well as chemical phenomena including
chemisorptions, thermal decomposition, and solid-gas
reactions (e.g., oxidation or reduction)
• In thermo-gravimetric analysis, the sample is heated in a given
environment (air, N2, CO2, He, Ar, etc.) at controlled rate. The
change in the weight of the substance is recorded as a
function of temperature or time.
• This plot of weight change against temperature is called
thermo-gravimetric curve or thermo-gram.
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5. Applications of TGA:
• From TGA, we can determine the purity and thermal stability of
both primary and secondary standard.
• Determination of the composition of complex mixture and
decomposition of complex.
• For studying the sublimation behaviour of various substances.
• TGA is used to study the kinetics of the reaction rate constant.
• Analysis of the dosage form.
• Oxidative stability of materials.
• Estimated lifetime of a product.
• TGA is often used to measure residual solvents, volatiles contents
and moisture.
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6. Differential Thermal analysis (DTA)
• PRINCIPLE: A technique in which the temperature difference
between sample and reference material at a constant heat
flow is measured as a function of temperature.
• The difference in temperature is called as differential
temp(∆T) is plotted against temp. or a function of time.
• Endothermic reaction: if sample absorbs some amount of heat
during phase transition then reaction is said to be
endothermic. Downward peak result
• E.g. Melting, boiling, sublimation, vaporization, de-solvation.
• Exothermic reaction: if sample released some amount of heat
during phase transition, then reaction is said to be exothermic.
Upward peak result.
• E.g. crystallization, degradation, polymerization
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7. Differential scanning calorimetry (DSC)
• PRINCIPLE: It is a technique in which the difference in heat
required to increase temperature of the sample & reference
material is measured as a function of temp. or time.
• Endothermic reaction: if sample absorbs some amount of heat
during phase transition then reaction is said to be endothermic.
Downward peak result
• E.g. Melting, boiling, sublimation, vaporization, de-solvation.
• Exothermic reaction: if sample released some amount of heat
during phase transition, then reaction is said to be exothermic.
Upward peak result.
• E.g crystallization, degradation, polymerization
• Glass Transition temp(Tg): Temp at which an amorphous polymer
or an amorphous part of crystalline polymer goes from hard ,
brittle state to soft or rubbery state.
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10. Application of DSC
• During pre-formulation, it is important to identify the polymorph
that are stable
• Thermal analytical system can be used for detection of impurities
in pharmaceutical ingredient by recording thermogram. This
curves could be then be compared with the curve of reference
standard . Any abnormal mass changes on TGA curve & irregular
endotherm or exotherm peaks on DTA or DSC curve would
indicate the presence of impurity.
• A sharp melting endotherm indicates the relative purity where as
broad asymmetric curve suggest impurity.
• DSC with the support of x-ray diffraction & infrared spectroscopy
are used as screening technique for the compatibility testing of
drug with excipient.
• The disappearance of the DSC peak of the drug is the proof of
complexation in solid state.
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11. X-RAY POWDER DIFFRACTION
• X-RAY powder diffractometry is used to characterize spray dried,
crystalline material & the binary mixtures.
• x-ray are diffracted & order of this diffraction is measured in
form of graph between spectra intensity vs 2ɵ (0-40)
• Diffraction occurs as a result of the interaction of radiation with
electron of atom.
• Because x-rays have wavelengths of about the same magnitude
as the distance between the atoms or molecules of crystal.
• Bragg’s law: When X ray is diffracted by the atom a relationship
between wavelength, angle of incidence light and distance
between successive atomic plane was established as:
nƛ = 2d sin ɵ
Where n = 1,2,3 … order of reflection
This equation is applied to calculate distance between the plane.
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12. XRD patterns of (a) crystalline (b) amorphous sucrose
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13. Application of X-ray diffraction:
• Structure of Crystals: The method is nondestructive and
gives information on the molecular structure of the sample.
• Polymer Characterization: XRD is the technique of choice to
identify different polymorphic forms of a compound. It can
also be used to identify the solvated and de-solvated
(anhydrous) forms of a compound, provided their lattice
structures are different.
• Identification Of Impurity: Presence of Additional lines on
the photograph of specimen, indicate the presence of
impurity.
• Degree of Crystalinity: XRD is widely used to determine the
degree of crystallinity of pharmaceuticals. First, it must be
possible to demarcate and measure the crystalline intensity
(Ic) and amorphous intensity (Ia) from the powder pattern.
𝒙 =
𝑰𝒄
𝑰𝒄+ 𝑰𝒂
x 100
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14. FT-IR SPECTROSCOPY
• A beam source of various IR wavelength light is sent through a beam
splitter, where half reaches a fixed mirror and half a mirror that
moves with a constant velocity.
• These two split beams are then reflected and recombined (now with
a path difference between the beams) to construct an interference
pattern reflecting the constructive and destructive interference of
the recombination.
• After, this interference pattern (or interferogram) is sent to the
sample, and the transmitted portion of the interferogram is sent to
a detector.
• After comparison with a reference sample beam spectrum in the
detector, a Fourier transform is performed to obtain the full
spectrum as a function of wavenumber.
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16. • Simple stretching: 1600-3500 cm-1 called functional group region
usually due to stretching
• Complex vibrations: 400-1400 cm-1, called the “fingerprint region”
usualy due to bending
Baseline
Absorbance/
Peak
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17. Application
1. Detection of impurities
IR spectrum of the test sample to be determined is
compared with the standard compound. If any additional
peaks are observed in the IR spectrum, then it is due to
impurities present in the compound.
2. Quantitative analysis
The quantity of the substance can be determined either in
pure form or as a mixture of two or more compounds. In
this, characteristic peak corresponding to the drug substance
is chosen and peaks for standard and test sample is
compared.
3. Identification of functional group and structure
elucidation
4. Studying the progress of the reaction
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18. THANK YOU
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