1. X-ray diffraction is used to study the interaction between drugs and polymers by analyzing their crystal structures. It works by detecting the interference pattern of X-rays scattered by the regular atomic structure of a crystal. 2. Key mechanisms of drug release from polymers include diffusion, degradation, and swelling followed by diffusion. Drug-polymer compatibility is important and can be studied using techniques like X-ray diffraction. 3. X-ray diffraction provides information on a material's unit cell dimensions, degree of crystallinity, and particle size by analyzing the diffraction pattern produced when X-rays interact with a crystal's atomic planes.

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Presented by-
Venkatesh G
M.Pharm (Pharmaceutics)
1st Semester ( 2020-22)
Sri Venkateswara University Tirupati
SVUniversity College of Pharmaceutical Sciences
Drug-Polymer
Compatibility
Study By XRD

2. 1. Introduction
2. Drug-polymer Interaction
3. Criteria followed in polymer Selection
4. Mechanism of Drug release from the Polymer
5. X-Ray Diffraction
6. Principle
7. Mechanism of X-Ray Diffraction
8. Applications
9. Biological Evolution
CONTENT
2

3. Polymers are long chain
organic molecules
assembled from many
smaller molecules called
as monomers.
Role of Polymers-
 In Manufacturing
of vials, syringes,
catheter's.
 In Manufacturing of
drug Formulations.
 Improve bioavailability of
drug
INTRODUCTION
3
Pharmaceutical
Polymers-

4.  Drug substances are usually in intimate contact with polymers.
DRUG - POLYMER
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INTERACTION
The molecular interactions between drugs and polymers in drug loaded polymer
micelles does not extend much beyond concepts such as “like-dissolves-like“ or
hydrophilic/hydrophobic. However, polymer-drug compatibility strongly affects
formulation properties and therefore the translation of a formulation into the
clinics. Specific interactions such as hydrogen-bonding, π-π stacking or
coordination interactions can be utilized to increase drug-loading. This is
commonly based on trial-and-error and eventually leads to an optimized drug
carrier.

5.  It must be soluble and easy to synthesize; must have a finite molecular wt.
 Should provide drug attachment and release sites for drug polymer linkages
 Should be compatible with biological environment, i.e. non- toxic and non-
antigenic
 Helps to avoid surprise problem during formulation process
 Should be biodegradable or be eliminated from body after its
function is over.
5
Criteria Followed in Polymer Selection

6. MECHANISM OF DRUG RELEASE
FROM POLYMER & INTERACTION
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⚫There are three primary mechanisms by which active agents can be
released from adelivery system: namely,
⚫Diffusion, degradation, and swelling followed by diffusion
⚫Anyorall of these mechanisms mayoccur in agiven releasesystem
⚫Diffusion occurs when a drug or other active agent passes through
the polymer that forms thecontrolled- release device.
⚫The diffusion can occur on a macroscopic scale as through pores in
the polymer matrix or on a molecular level, by passing between
polymerchains

7. Drug delivery from typical reservoir
devices: (a) implantable or oral
systems, and (b) transdermal systems.

8. X – RAY
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DIFFRACTION
Contd….
X-Ray Diffraction is a Phenomenon
in which the atoms of a crystal, by
virtue of their uniform spacing, cause
an interference pattern of the waves
present in an incident beam of X-
Ray.
(or)
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.

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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.

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Bragg’s Law
Bragg’s Law States that the
“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”.
• The path difference between ray 1 and
ray 2 = 2d Sinθ
• For constructive interference: nλ = 2d
Sinθ This is called Bragg’s Equation.

11. Mechanism of X-Ray Diffraction
X-RAY DIFFRACTION METHODS :
These are generally used for investigating the internal structures and
crystal structures of various solid compounds. They are :
4. Powder method
3. Rotating crystal method
2. Bragg’s X-ray spectrometer method
1. Laue’s photographic method : a) Transmission method
b) Back reflection method

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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.
1. Laue’s photographic method
a) Transmission method
:

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Contd….
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

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 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

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 Laue-beam of x-ray-crystal-emitted x-ray obtained on photographic plate-using
photograph-brag analysed structures of crystals of Nacl, Kcl, and Zns -brags
equation.
 Single plane generates several diffraction lines-sum total of diffraction lines gives
diffraction patterns-from the pattern we can deduce different distances between
planes-angle between planes in each of three dimensions.
2) The Bragg’s x-ray spectrometer method:

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 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)

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 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 angle ѳ
 Peaks are obtained. peaks corresponds to Bragg’s reflection
 Different order glancing angles are obtained with known values of d and n and
from the observed value of ѳ , λ can be measured.
Contd….
Working :

18.  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

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3) ROTATING CRYSTAL 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.
1. Complete rotation method :

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 The crystal is oscillated at an angle of 15° or 20°
 The photographic plate is also moved back and
forth with the crystal
 The position of the spot on the plate indicates the
orientation of the crystal at which the spot was
formed
2. Oscillation method :

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4) POWDER CRYSTAL METHOD:
 X-ray powder 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. Fine powder is struck on a hair with a
gum, it is suspended vertically in the axis of a cylindrical camera.

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 When monochromatic beam is allowed to pass different possibilities may
happen
1. There will be some particles out of random orientation of small
crystals in the fine powder
2. Another fraction of grains will have another set of planes in the
correct positions for the reflections to occur
3. Reflections are possible in different orders for each set
 If the angle of incidence is ѳ then the angle of reflection will be 2ѳ If the
radius is r the circumference 2πr corresponds to a scattering angle of 360°
Ѳ=360*1/πr
 From the above equation the value of ѳ can be calculated and substituted in
bragg’s equation to get the value of d

23. APPLICATIONS
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1. Structure of crystals :
a) X-Ray pattern of salt Nacl
b) X-Ray pattern of salt Kcl
c) X-Ray pattern of mixture of Nacl & Kcl
d) X-Ray pattern of a powder mixed crystal
of Nacl & Kcl
2) Polymer characterisation :
 Determine degree of crystanillity.
 Non-crystalline portion scatters x-ray beam to give a continuous background
(amorphous materials)
 Crystalline portion causes diffraction lines that are not continuous. (crystalline
materials)

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3) Particle size determination :
Spot counting method: v=V.δθ.cosθ/2n
v = volume of individual crystallite
V = total volume irradiated
N = no. of spots in diffraction ring
δθ = divergence of x-ray beam
Biological Evolution :
Biological Compatibility : Should be Non-Toxic
Should be taste less
Should be odour less
Should be Non-Irritating
Should be Insoluble in saliva

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