X-RAY DIFFRACTION

MPHIL PHARMACEUTICS 2017-19

INTRODUCTION
Definition:
The atomic planes of a crystal cause an incident beam of X-rays to interfere with one another as
they leave the crystal. The phenomenon is called X-ray diffraction.
It is a novel & non destructive method of chemical analysis and a variety of x –ray
techniques are available in practice.
These are : X – Ray Absorption : X-ray diffraction : X-ray Fluorescence

X – ray diffraction
“ Every crystalline substance gives a pattern; the same substance always gives
the same pattern; and in a mixture of substances each produces its pattern independently of the
others”
The X-ray diffraction pattern of a pure substance is, therefore, like a fingerprint of the
substance. It is based on the scattering of x-rays by crystals.

WHY XRD
 Measure the average spacing's between layers or rows of atoms
 Determine the orientation of a single crystal or grain
 Find the crystal structure of an unknown material
 Measure the size, shape and internal stress of small crystalline regions

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X-RAYS
1. X-rays are short wave length electromagnetic radiations produced by the deceleration of
high energy electrons or by electronic transitions of electrons in the inner orbital of atoms
2. X-ray region 0.1to100 A˚
3. Analytical purpose 0.7 to 2 A˚

PRINCIPLE
X-ray diffraction is based on constructive interference of monochromatic x-rays and a
crystalline sample. These x-rays are generated by a cathode ray tube, filtered to produce
monochromatic radiation ,collimated to concentrate and directed towards the sample. The
interaction of incident rays with the sample produces constructive interference when conditions
satisfy Bragg’s law.

 Constructive interference of the reflected beams emerging from two different planes will
take place if the path lengths of two rays is equal to whole number of wavelengths”.
 For constructive interference;
nλ=2dsin this is called as BRAGG’S LAW

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ESSENTIAL PARTS OF DIFFRACTOMETER
 X-ray Tube: the source of X Rays
 Incident-beam optics: condition the X-ray beam before it hits the sample
 The goniometer: the platform that holds and moves the sample, optics, detector, and/or
tube
 The sample & sample holder
 Receiving-side optics: condition the X-ray beam after it has encountered the sample
 Detector: count the number of X Rays scattered by the sample

INSTRUMENTATION
 Production of X-Rays
 Collimator
 Monochromator
 Filter
 Crystal monochromator
 Detector
 Photographic methods
 Counter methods

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XRD METHODS
These are generally used for investigating the internal structures and crystal structures of various
solid compounds.
These are:
 Laue photographic method
a)Transmission method
b)Back reflection method
 Braggs X-Ray spectrometer
 Rotating crystal method
 Powder method

a)Transmission Laue method

In the transmission Laue method, the film is placed behind the crystal to record beams which are
transmitted through the crystal.
One side of the cone of Laue reflections is defined by the transmitted beam. The film intersects
the cone, with the diffraction spots generally lying on an ellipse.
 Can be used to orient crystals for solid state experiments.
 Most suitable for the investigation of preferred orientation sheet particularly confined to
lower diffraction angles.
 Also used in determination of symmetry of single crystals.

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b)Back-reflection method
 In the back-reflection method, the film is placed between the x-ray source and the
crystal. The beams which are diffracted in a backward direction are recorded.
 One side of the cone of Laue reflections is defined by the transmitted beam. The film
intersects the cone, with the diffraction spots generally lying on an hyperbola.
 This method is similar to Transmission method however, black-reflection is the only
method for the study of large and thick specimens.
Disadvantage:
 Big crystals are required
 Crystal orientation is determined from the position of the spots. Each spot can be
indexed, i.e. attributed to a particular plane, using special charts.
 The Greninger chart is used for back-reflection patterns and the Leonhardt chart for
transmission patterns.
 The Laue technique can also be used to assess crystal perfection from the size and shape

Bragg’s x-ray spectrometer method

 A-anti cathode
 B-B’ – Adjustable slits
 C-crystal
 E-ionization chamber
 One plate of ionization chamber is connected to the positive terminal of a H.T Battery ,
while negative terminal is connected to quadrant electrometer(measures the strength of
ionization current)
Working:
 Crystal is mounted such that ѳ=0° and ionization chamber is adjusted to receive x-rays
 Crystal and ionization chamber are allowed to move in small steps
 The angle through which the chamber is moved is twice the angle through which the
crystal is rotated
 X-ray spectrum is obtained by plotting a graph between ionization current and the
glancing angleѳ
 Peaks are obtained.peaks corresponds to Bragg’s reflection

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  Different order glancing angles are obtained with known values of d and n and from the
observed value of ѳ , λ can be measured.

DETERMINATION OF CRYSTAL STRUCTURE BY BRAGG,S LAW

 X-Rays falls on crystal surface
 The crystal is rotated and x-rays are made to reflect from various lattice planes
 The intense reflections are measured by bragg’s spectrometer and the glancing angles for
each reflection is recorded
 Then on applying bragg’s equation ratio of lattice spacing for various groups of planes
can be obtained.
 Ratio’s will be different for different crystals
 Experimentally observed ratio’s are compared with the calculated ratio’s ,particular
structure may be identified.

ROTATING CRYSTAL METHOD

1- Complete rotation method:in this method series of complete revolutions occur

 Each set of a plane in a crystal diffracts four times during rotation
 Four diffracted beams are distributed into a rectangular pattern in the central point of
photograph
2.Oscillation method:the crystal is oscillated at an angle of 15° or 20°
 The photographic plate is also moved vack and forth with the crystal
 The position of the spot on the plate indicates the orientation of the crystal at which the
spot wasformed

What is Powder X-ray Diffraction (XRD)

Powder X-ray diffraction (XRD) is a rapid analytical technique primarily used for phase
identification of a crystalline material and can provide information on unit cell dimensions. The
analyzed material is finely ground, homogenized, and average bulk composition is determined.

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Fundamental Principles of X-ray Powder Diffraction (XRD)
 X-ray diffraction is now a common technique for the study of crystal structures and
atomic spacing.
 X-ray diffraction is based on constructive interference of monochromatic X-rays and a
crystalline sample.
 These X-rays are generated by a cathode ray tube, filtered to produce monochromatic
radiation, collimated to concentrate, and directed toward the sample. The interaction of
the incident rays with the sample produces constructive interference (and a diffracted ray)
when conditions satisfy Bragg’s Law (nλ=2d sin θ).
 This law relates the wavelength of electromagnetic radiation to the diffraction angle and
the lattice spacing in a crystalline sample.
 These diffracted X-rays are then detected, processed and counted.
 By scanning the sample through a range of 2θangles, all possible diffraction directions of
the lattice should be attained due to the random orientation of the powdered material.
 Conversion of the diffraction peaks to d-spacings allows identification of the mineral
because each mineral has a set of unique d-spacings. Typically, this is achieved by
comparison of d-spacings with standard reference patterns.
 All diffraction methods are based on generation of x-rays in an X-ray tube. These X-
rays are directed at the sample, and the diffracted rays are collected.
 A key component of all diffraction is the angle between the incident and diffracted rays.
Powder and single crystal diffraction vary in instrumentation beyond this.

APPLICATION OF XRD
 XRD is a non destructive technique to identify crystalline phases and orientation
 Obtain XRD pattern ; Measure d-spacings ; Obtain integrated intensities ;
 Compare data with known standards in the JCPDS file
 To determine structural properties:
 To measure thickness of thin films and multi-layers*
 To determine atomic arrangement
 Detection limits: ~3% in a two phase mixture; can be ~0.1% with synchrotron radiation
 The electron density and accordingly, the position of the atoms in complex structures,
such as penicillin may be determined from a comprehensive mathematical study of the x-
ray diffraction pattern.
 The powder pattern may be thought of as finger print of the single crystal structure, and
it may be used conduct qualitative and quantitative analysis.
 XRD can also be used to determine whether the compound is solvated or not.

With specialized techniques, XRD can be used to:

 Determine crystal structures using Rietveld refinement

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  Determine of model amounts of minerals (quantitative analysis)
 Make textural measurements, such as the orientation of grains, in a
polycrystalline sample.
 X-ray powder diffraction is most widely used for the identification of unknown
crystalline materials (e.g. minerals, inorganic compounds). Determination of unknown
solids is critical to studies in geology, environmental science, material science,
engineering and biology. Other applications include
 characterization of crystalline materials
 identification of fine-grained minerals such as clays and mixed layer clays that are
difficult to determine optically
 determination of unit cell dimensions measurement of sample purity

Applications of Powder X-Ray Diffraction in Science and Technology

Polymorph study
PXRD is helpful in identification and characterization of polymorph, monitoring the stability,
method development and validation for identification and quantification of drugs in
Pharmaceutical Industries. X-rays are partially scattered by atoms when they strike the surface of
a crystal. The part of the X-ray that is not scattered simply passes through the next layer of
atoms, where again part of the X-ray is scattered and part of it passes through to the next layer.
This causes an overall diffraction pattern, similar to how a grating diffracts a beam of light. In
order for an X-ray to diffract, the sample must be crystalline and the spacing between atom
layers must be close to the radiation wavelength.
Variable Temperature and Relative Humidity study by PXRD
Solid phase transitions such as polymorph inter-conversions are routinely examined by X-ray
diffractometer using variable temperature sample stages (VT-XRD). Both subambient and
elevated temperature stages are available that can help to study the sample behavior at variable
temperature conditions.
Use of PXRD in Pharmaceutical industry
XRD is the key technique for drug analysis. It serves a major role in all stages of drug
development, testing and production. It is an essential part of analytical research and
development, quality control of the active ingredients, excipients and final products. Minor
changes may cause major batch-to-batch inconsistency that may cause critical problems and lead
to problems in the manufacturing of the pharmaceutical dosage form, the quality of the
formulation, the bioavailability and drug stability.
The materials ranging from Active Pharmaceutical Ingredients to finished dosage forms have to
be properly screened by XRD as it ultimately cause changes in diffraction patter and affects the
bio-availability

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Use of PXRD in Nano and Material science
The term particle size and crystallite size refer to two distinct properties in a material. Particles
comprise of several small crystallite. Crystallite size is the fundamental property of materials.
Properties of nanomaterials depend on crystals size and not particle size. PXRD can measure
millions of crystals and accurately determine the size distribution of nanomaterials. It can be
widely used for studying the nature of polymers and composites in Material Science
PXRD use in Forensic studies
PXRD is useful in trace analysis. It can be used to contact traces of paint flakes, hair, glass
fragments, stains of any description and loose powdered materials. Identification and comparison
of trace quantities of material can help in the conviction of a suspect of his involvement in a
crime
Crystallinity study by PXRD
The XRD analysis of crystalline compounds gives a diffraction pattern consisting of a well-
defined, narrow, sharp and significant peak while amorphous materials do not give clear peaks
rather the pattern has noise signals, smeared peak or it can have some short order bumps. Many
polymers depict semi-crystalline behavior and produce halo pattern. Powder XRD can be used to
determine the crystallinity by comparing the integrated intensity of the background pattern to
that of the sharp peaks. Different scientists have reported variable methods to find out the
percentage crystallinity and crystallinity index.

Strengths and Limitations of Powder X-ray Diffraction (XRD)

Strengths
 Powerful and rapid (< 20 min) technique for identification of an unknown mineral
 In most cases, it provides an unambiguous mineral determination
Minimal sample preparation is required
 XRD units are widely available
 Data interpretation is relatively straight forward
Limitations
 Homogeneous and single phase material is best for identification of an unknown
 Must have access to a standard reference file of inorganic compounds (d-spacings, hkls)
 Requires tenths of a gram of material which must be ground into a powder
 For mixed materials, detection limit is ~ 2% of sample
 For unit cell determinations, indexing of patterns for non-isometric crystal systems is
complicated
 Peak overlay may occur and worsens for high angle 'reflections'

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Conclusions
 Advances in PXRD instrumentation and software have improved the efficacy of
pharmaceutical drugs, efficiency of solid state characterization and rapid analysis of
composites and materials. Variable temperature and humidity techniques are especially
powerful in understanding structural changes of pharmaceutical drugs to enhance the
stability and screen the drug substances under variable conditions. Ongoing
developments involving structure determination directly from PXRD are encouraging to
determine the crystal structures of new synthesized compounds and in pharmaceuticals.
 Powder X-Ray Diffraction technique is a key analytical technique to serve the growth
and development of Science and Technology.

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