Advanced Pharmaceutical Analysis

1. X-Ray Crystallography
Nuzhat Tasnim Amin
Lecturer
Dept. of Pharmacy
Varendra University

2. X-ray Diffraction
• X-ray diffraction is a method of X-ray crystallography, in which a
beam of X-rays strikes a sample (crystalline solid), land on a piece of
film to produce scattered beams.

3. X-Ray Crystallography
• X-ray crystallography is used for determining the atomic and
molecular structure of a crystal using x-ray diffraction method.
• From the angles and intensities of the scattered beams, a
crystallographer can produce a three-dimensional picture of the
density of electrons within the crystal.
• From this electron density, the positions of the atoms in the crystal can
be determined, as well as their chemical bonds, their disorder and
other information.

4. Principle
• The technique of single crystal X-ray crystallography has some basic steps.
The first and usually most difficult step is to produce an adequate crystal of the
studied material. The crystal should be sufficiently large with all dimensions
larger than 0.1 mm, pure in composition and regular in structure, and have no
significant internal imperfections such as cracks or twinning.
• The crystal is subsequently placed in an intense beam of X-rays, usually of a
single wavelength, to produce regular reflection pattern.
• The angles and intensities of diffracted X-rays are measured with each
compound having a unique diffraction pattern.

5. Principle
• Previous reflections disappear and new ones appear along with the
gradual rotation, and the intensity of every spot is recorded at every
orientation of the crystal.
• These collected data are combined computationally with
complementary chemical information to obtain a model from the
arrangement of atoms within the crystal.
• The final refined model of the atomic arrangement is called a crystal
structure.

7. Application
• Identification of unknown crystalline materials.
• Determination of unknown solids.
• Characterization of crystalline materials.
• Identification of fine-grained minerals that are difficult to determine
optically.
• Measurement of sample purity.
• Determine crystal structures.
• Characterize thin films samples.

8. Limitations
• Homogeneous and single-phase
material is best for identification
of an unknown.
• Requires tenths of a gram of
material which must be ground
into a powder.
• For mixed materials, detection is
quite difficult.
• Peak overlay may occur and
worsens for high angle
'reflections'

9. X-ray Source
• X-rays used for diffraction are electromagnetic waves with short
wavelengths in the range 0.05 – 0.25 nm.
• To produce X-rays for diffraction purpose, a voltage of about 35 – 50
kV is necessary and applied between a cathode and an anode target
metal, both are contained in a vacuum.

10. Goniometer
• Diffractometer circle is also known as goniometer circle.
• Goniometer is the central component of an x-ray diffractometer and
contains the specimen holder
• It has arm to which the x-ray source and detector are mounted.
• Usually, goniometer is vertically mounted but those used for thin film
studies are horizontally mounted.
• A goniometer is an instrument that either measures angle or allows an
object to be rotated to a precise angular position.

11. Specimen
• Crystalline materials in forms of bulk,
powder, sheet or thin films can be
analyzed.
• For powder specimen, a thin layer of
crystalline powder is spread on to a planar
substrate.
• The grain size of the powder should be less
than 50 μm.
• If grain size smaller than 1 μm, broadening
of the peaks in the diffraction pattern
occurs.
• If a mixture of two powders to be
characterized, they must be thoroughly
mixed.

12. X-ray Detector
• In the diffractometer, the intensity of the diffracted beam is measured
directly by an electronic x-ray detector.
• They are many types of detectors, but they all convert the incoming x-rays
into surges or pulsed of electric current.
• There are three main types of detector used in x-ray diffractometers.
a) Proportional
b) Scintillation
c) Semiconductor
• For instrument dedicated for powder works, a proportional detector is
probably used.

13. Factors Depending on X-Ray
Diffraction Pattern
• A typical x-ray diffraction pattern consists of a series of peaks with
various intensities.
• Each peak or reflection in the diffraction pattern corresponds to the x-
rays diffracted from a specific set of planes in the specimen.
• The positions of the peaks in an x-ray diffraction pattern depend on the
crystal structure of the materials.
• Number of peaks depend on the symmetry of the crystal structure.
Example: Cubic crystal structure has fewer peaks while hexagonal
structure has more peaks in its diffraction patterns.

14. Result Analysis
• Most commercial software allows the user to compare standard pattern
(from database) with experimentally observed patterns-rapid matching
and identification.
• Hight of Peak
• Width of Peak
• Intensity of Peak
• Spot count
• Angle of rotation

15. Bragg’s Equation

16. THE END