1. The document discusses X-ray crystallography and summarizes key concepts about X-ray production and crystal systems. It explains that X-rays are generated when high-speed electrons interact with matter and that three components are needed: an electron source, means to accelerate electrons, and a target material. It also describes the six basic crystal systems classified by their crystallographic axes and angular relationships.

1. Written By
Department of Pharmacy
University of Rajshahi
Rajshahi-6205, Bangladesh

2. ".......!
Md. Irnr-ari Nu» Maru·k..
'Roll ~ 09055'33 ~
Mob
'
/
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3. Kushal. -I Ox-Ray Crysta{fograyfi=-y__
,;--Absorption energy:
The total energy in a molecule is the sum of energies associatedwith the transitional,
rotational, vibrational and electric motion of the moleculeor the electrons and nuclei in
"'the molecule.ri.e.
E.:::E+E+E+Ez: r V IW
a. Transitional energy (Etl is associatedwith the velocity of the molecule as a whole.
b. Rotational energy (Erl associatedwith the overall rotation of the molecule.
c. Vibrational energy {Ev) associated with the vibrations of the atoms within the
molecule.
d. Electronic energy {Em) associatedwith the motion of electrons around the nuclei.
4 Wave number:
The wave number is the number of wavelengths per unit of length covered. It is the
reciprocal of the wavelength. Mathematically; a= 11;._
The following terms are usedto describe electromagnetic radiation.
Tne WClNl?~{h ol. C' l..R'lfff c-' r:.fviQ 13 i hf2 .MW,a.... f,daree' ~o!JLU!Pd won('.! 'ilui :,~,
, ~&- <../""4 Wavelength: 1?"crpo1al•n b-eiwel/7!. -(1.()o pohJ< wlv'di aJl$ ,:,., nhC15, cm odjacc'Tl1 Lvc,. .. ':> ..
Gi S The wavelength is defined as the difference between the two successive crests or i
troughs of a wave. It is denoted by the Greek letter "A (lambda). It is expressed by
centimeters or meters or angstrom (A) units.
1A=10"10m, 1nm=10"9m, lµm= 10-6m, lmm= 10"3m
4- Frequency:
The frequency is the number of waves which pass a given point in one second. It is
denoted by the letter o (nu) and expressedin hertz (Hz).
Mathematically, u = c/;A, where, c = velocity of EMR
.vlv-:'1..
Many drugs absorb electromagnetic radiatio a helps to determine the quantity and ? die .,..1 -rtt ,
nature of the drug 1 n a dosage for"(!Jn a reaction vessel r; n a biological system. Radianf
energy is the energy transmitted as electromagnetic radiation. The sun is the most
important source of radiant energy.
i
l
1
X ray Crystallography
r;:,p..iu in .JN. fc· '
Electromagnetic radiation: St 'YT'O be ~.)crm red o emu1t:J_J pnoJJ0r:JcJ1ri3 ;,., ,w._,
~Energy can be transmitted through the spaceby electromagnetic radiation Electromagnetic
~ffed b~1
radiations areRsoeiameQjbecausethe~/contain the waves whicJi}have;electrical and magnetic
I-n EM 1__;.;:
properties-An object sendsout energy waves when its particle.move up or down or vibrate
continuously, Such a vibrating particle causes an intermittent disturbance-which constitutes
71w5 .
a wave. kwave conveys energy from the vibrating object to a distance place. The wave
travels at right angel to the vibratory motion of the object .
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4. ,}
I
)
If
I
t
;
J
.l
If
f
f
I
. J
Kusha! -
~.-----
I
L
.--·· ~
I
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!
r
a.~. - "'crt' "&~_, ~ ~
X-'Ray Crystaffograyliy
3. Hexagonal system:
This system includes those crystals which are referred to
three equal axes lying in one plane and intersecting at angel
of 60° and a fourth axis, either longer or shorter and
perpendicular to the plane of other three.
The equai axes are, a=btc and a= ~ =90° and v = 120°.
2. Tetragonal system:
This system inciudes those crystals which are referred to three
perpendicular axes, two of them are equal in length and one is
shorter or longer compare to them.
Here, a=b=c and a= 13 = y = 90°.
1. Isomeric system:
This system includes those crystals which are referred to three
mutually perpendicular equal axes. this isomeric system is also
known as cubic crystal system.
Here, a=b=c and a= 13 = v = 90°.
<L.0. - ,V'"'e_.1,<!.se. c....~'2., C'.. C
.....erystals: f-"'
O/Y''.)tLWr
Al'l:.ide.al>crystal is ~.i:egu-lar polyhedral solid bounded by plane faces which represents an
" . ulan. ru: reaJin5 3 D .9.,,,,,.,.,.,t-..:r,,J po..+I <>r-,-, ·
extended array of atoms arranged in a Clefklit:e ordeoln all directions. Such a crystal contains
a unit cell or a unit of structure;2-~petition of which · three dimension~ produces the
crystal :,Each unit cell for a specific crystal is the same size and shape and contains same
number of atoms similarly arranged) Crystal varies in the angular relationships and
symmetry. (9.'.-,the basis, a crvstal is gfassified into one of six basic crystal systems. Each
system is defined in terms of the crystallographic axes, which are imaginary lines used to
describe the position of the plane faces in space. The systems are defined as follows·'
and light.
---------------- Gi1101JJ1>d S+.:1~e
UV energy. . w• ··Uuh 10 IC c, r:thri ·, -~ fut/') n C!· >
An excited electron returns to the ground statei.ir:i-a.be-l:lt-1-0-94e--10-8WG -energv is new
reieased to compensate for the energy absorbed by the system. If the rWcf1~CITW1returns to
the ground state b' ~a second excited state, energy is released in the form of heat
E1 i;...,.,.;-l ~d Sfco-' c
~
2
f 11oc:lt0+c.,, _( P_h_c_•--,, _
When a moiecuie absorbs radiant 0nergy an eiectron or eiectrons wiii be raised to a higher
+ hal ~ tl/11 ~ i-f ,.
energy level if the energy requlrernenwis equal to the energy of the incoming photon. Such
:i.k -1>-.•.n1~n2 1~ 1/f
electrons are found in.conjugated double bonds.ssaturated molecule therefore hot absorbs
gr /I
10, er>· an emcn j y 0 ~ I co I ri rr ll ! ('
~y•y,cJI
rrnaJ tJ(' ll(..lp I u11rcl I ,rf J.•.H r, ~;, ,, I f,, t<' rol JV',. . ) r, r
- - I
Y->""
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5. L
@) 3 CY(JStcU ll.lXIS one ru!JAf ~~ Jo ~ oH1e.r- ~'jj {UA) ~l:h.
'-rll '3 ~e CV~-•t:U p'lame ':1 srme.4:_~ OJU- prurallel to ;1°/c_jtce5 I
~ ! MJ jixeJ ·":f tha•" rrJ-iu.h'cm j o:J#J/.D.!IIW.f',,;e a#< '
/~ ~ j _L Bm..B-th- ~ a= b=c . I
; .· - -~ 'Ang IL : a= f3 :: Y ::: 9 o I
. _t.® f3crysic:J~}s ans: ~. ~~ do ~di ~t~ ·Two j-thom1al1ll
1
d ~ al) dtlR- ·hovn'-i:J:mlPJ o.¢1'5 beJ"':j ec.ru.a1 · __
' ' ~ -nu- 3~ ,._ e . VlVPb'CA.1 ~s 1'r> ~U"> 01'> e M'f)-t}iD,n i::hwti -t~
r :1 gl l ei t~ --f:!.o o •
':~ t t L.~ th-: a.::= b j- c. .
; !<- ~ ft-n:9 le- ~ oc = f3 =- v= go
, :~ S cry"{«) -~ alU ru;1J ""If'- do e<>d •-thM> b.d--;;H.,,;;_ti 1 . ~fj- cLjpeml- ~-Hw. _
<' ~ 9~·1.<~ p~j s1')'Y)~ ~ d <30··
-~ j· L~rh..: a* b:t e.
! 0 ilrrt-_E~ ! .o: = (3 == ,v -z: 00·
I
I
I I
I
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6. Kushai -
atomic
model
electron
·' density ma,p
diffraction
pattern
..c
fl
E
GI
c
i
crystal-~~~<'
x-rays'
:J '. {c ,/ '(':)(1 I/
J
3 . ~ . -, h f I ' Cl f l.( 11// if
X-'Ray Crysta{fograyfiy
When any electron with high velocity strikes a metal, an
unknown highl;Jpenetrating radiation emits, which is
known as x-ray. There are several properties of x-ray
'"which makes it useful-radiographic inspection. X-rays
are the sameform of energy as visible light. Like light it
is reflected and refracted when it pass the glass,lens or
other medium. Although the properties of x-ray and
visible lights are theoretically similar; the difference in
application make it more convenient to consider x-ray
as being different, since their observable effects are
quite different from those of light-0some general
2i1CJJroperties of x-ray are as follows:
~
1. It is invisible to human,
l '<
2. It propagates in straight line irtfree space. J ..,
3. It propagates at a velocity of 3*108m/sec. 1 l' 1
~ J. x:- ·/J.if , 0 f r · ,
5. Monoclinic system:
This system includes those crystals which are referred to
three unequal axes, two axes are perpendicular to the third
axis but not to each other. The two axesare a & c and third is
b. Here,a;tb;tcand a= ~ =90° and v = 120°.
..~.~.- c.~~014'2._~0~ J(c!Oi", ~'1~.q_(CIVJc,
6. Tric/inic system:
This system includes those crystals which are referred to three
unequal axes intersecting ~t oblique and obtuse angels. The
axesare a, band c. Here,a:;tb:;tc and a :;t 13 :;t 90°.
..:'>-·-····
4. Orthorhombic system:
This system includesthose crystals which are referred to three
mutually perpendicular axesof unequal length.
Here aebecand a= 13 = v = 90°.
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7. A. A source ofelectron.
vf -1. !.-<
Each matter is made up +th atoms and.atoms
have electrons that orbit around the nucleus in
shelik. These electrons are needed to get free of
r e_oof"'.d
their orbit. When a current is passing through a
bC
piece of conductive wire, the wire will11heatdup
due to the resistance. The heat of the wire
,,...-:>.J !W C l.L ( ./ C'r'""-li.;.
excites #ie)efectrons and-thev-break away from
J~i·c kt~
the wire to expwd the energv-break-up from the
heat of the current. When the energy of the
_....
~ (l)
I
co
ro
~
c,
X-'Ray Crysta{fograyfiy Kusha!
-11~11
' lh d f1i>dnG"()p<
lc
-7 ~<
-~e-
>Q ~
I), A
:.. ( . ' And).d.Q•S... "l r . ~' , ,.,
electron is expended, it will return to the wire to
r,e1 rv e -V<
become heated again. So this heated wire ilG:t.a5=<8 source of electrons.
There are two different atomic processes that can produce x-ray photons:
a-?·s~emsstfa.::t11ung'mechanism co ~~(
b. K-shell emission
. , J
'.J '-i j c t
X-ray produced by Bremsstrahlung mechanism is the most.usefu] for medical and industrial
applications.
.i
j
.interaction appears as electromagnetic energy known as X-radiation.
!
t1
'
, .
a. A source of electron
ll
b. A mean of accelerating the electrons atlhigh speed.
c. A target material to receive the impact of electron and interact with them.
·:_ .; • · ~ : .f:hR- ~Jth.2.r"r>
X-ray5are generated whentfree electrorggive up some there-energywhen they interact with
the orbitakelectrons or nucleus offatom~ The energy given up by the electro11;~ this
:J. · 1 - 9. "Able to damage or kill living cells and to produce genetic mutationt
.___,Production.$ ofx-ray:
/ To generate x-ray the following three things are-needed:
6. x-rav has enerzv between HJ·i:jgJ:t-f-y·1KeV and 50~ eV. 1
, ~ • f '../_LL
7. !t stimulates fluorescence and phosphorescence in.same material. 11 '
8. It is capable of ionizing gases and c;.l:iar:ging the electrical properties of some liquidI
( i ,,.'
and solids
4. it consists of transverse eiectromagnetic vibration a~oes-i~g-ht.-r~ ·
.. • r , I I ,;,
5. In special cases it is reflected, diffracted and polarized as light.
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8. .,
't~
1
I
(. )
(.... v ( h{ll' '( : :
)~
~
'
Kushai -- X-Ray Crysta[fograyfiy
~ High voltage power supply is an important component of an x-ray generation system.The
Fi fJOIN•I
filament usesf relatlvelv-small voltage-supply to~cause small currents (mV) in the filament:
while the anode of the tube requires a la-Fge}supplyto maintain high positive charge for -i r
acceleration of-electrons,
b. High voltage power supply:
·4'. The target matter provides the means
of electron;.tn'lgration (bombardment).
~ The target is commonly made"'"trom(W)
Tungsten £and other materials lik~
C r- I=< tl • ~ ·
cobalt, iron or copper, - : ( t rv
-4.. The material must--h~.lle high atomic
'I.
massfor/electron interactionz .
'* .Low density electron does not provide
sufficient density tor}interaction.
~Factors affectinq-production ofx-ray: 71~ t:" t• 'd J-o r l-t.« r 1 fr ./ Ifie ;)'f')(rlu I
a. Effecta/density of the target matter:
r . t ~ ) ; •
.-, The electronscan be absorbed by an atom of target/and its energwtransferred i6'to
the atom.c- '11. rct , ,,.
• The energy of the electron can cause another electron to be knocked out of its
energy shell.. ~ L
-4. Radiatio'n'can be produced in .aft--ofthese cases,but the energy of the radiation can('
be different. .
When the electrotehits the target matter several things can be happened:
lh ' ·I
For-acceleration of the electrons/that were generated from the cathode unittare allowed to
" a ~
be attracted by an anode in a short distance. When-voltage is applied to this anode (i.e.
.. . .,Lr.i ,
highly positive_fhargeJthis actmuch like as a magnet, the}()nfy~ttracQree electrono. r .J )
JI T ,,._../.
I
C. Role of target material to interact with electronic
. .[IC '- · · rv
To interact witfvelectrons the target material is placed between-two electrodes. Sometimes
anode itself can be used as J-~~rget~ hlg~4;~ita"ge'~-~ay generator'a special target matter
(tungsten) is usually embedded into the anode. Thisgives the electron a suitable material to
interact with and produce X-rays.
B. Acceleration of electrons at high speed:
., .
/ +
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9. n ,.
X-'Ray Crysta[fograyfiy
J-1<-/ Cl l . J
: (?
- dsinO
.
• • • "°(!)
OJ)
ro
0..
Kushai
-r. >
/'
/
1M ./
jA ..
t>
••
The rays of the incident beams are
aiways in phase and parallel up to the
point- at which the top beam strikesI .
the top layer at atom A. lhe second
beam is continuous to the next laver
, ..
where it is scattered by· atom B.1he
second beam must travel the extra
-p.lang..s- which are parallel to one
~"'° p U"llt[ (I .
another and am oµerat-eci by~the'fixed
spacing d. ,I beam of x-ray (mono-
1 I .chromic wave) of wave length A is
directed to the?e planes att~ngel 9 ·
.{'
2. The path length difference is equal to an integer number of-wavelength-
!.) JJ)
J I I rff( p
r 10 Consider a crystal containing-faces 0f-
1. Theangelof incidence is equal to the angel of scattering
Bragg's Law:
I 1_-l .
When~x-raysare scattered from a' crystal lattice, peaks of scattered-intensitv are absorbed
which correspondsto the following conditions:
(!I'> t .J"-{ I
Diffraction occurs as radiatio interacts with a regular structure-whose repeat distance is
about the sameas the wavelength. e.g, light ca~1~iffracted by a gr~ding-having scribed lines,)
spread on the order of~ewthousand.angstroms, about the wavelength of light.
'-,I l l 1J.
X-rays hav~ wavelengths '" the order of few an:stroms, the ~~me as ~ypical int~ornic
distances :n crystalline solids. That means X-ray.)can be dittracted trom rninerats,« by
definition,are crystalline and have regularl'f expeetlng-atomlc structure.f )
)r.er·r l -~., ,. ,
When certain geometric requirements are met ~ay/scatteredfrom the crystalline solid.
- _.,,,con< .. n,.,,J(J 1
(And)¬ onstruct1vely11nterfere,producing a diffracted beam. In 1912 W.L. Bragg recognizeda
predictable relationship among several factors. These are as follows:
1. The distance between two similar atomic planes in a i!l{Xe'r~1I ((interatomic spacing)
which we call d-spacingand measure in angstrom.
2. The angel of diffraction, which we call the a angel,('l:S measure in degrees. For
practical reason the diffractometers'measure-theangeltwice that of the theta angel
i.e. 28.
3. Thewavelength of the incident x-rav radiation1A.equa!to 1.54A.
-{ie;hw~Jn
X-ray diffraction & Bragg's law: 1JfP ~ I 0
'( i I '1
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10. . . -'
~. --
j
,../
.., r
I '
Jl
.1'_
.. '
!
'C' .. -f •
1
. 'Deftc.{OY'I
•
E:Le.c.:bat'c Votfaee H(gh vo/t~e X- ~a'/ t5/it ...•. fowe.r> S fab,' lizer
-61ene yia ti:rr Take
If . '
Ca/lime~u·
f.
fa..blltre.Y">
) .... 'f
'
;
An;ptf~r Sea.I er» 'Ppfnfer>I
-,
t·
./ :.;;~~~~~~~J .; ~'
Itnsfrwm~'ffl'I ~· ..:!k]'llh~ patr.1--s
a)X-~ (jemM~ /~~/x~~ tttlo~
d)A-na~?t~ ~6~
e) Detec.-f:_o-p ----4':.
b)Coll 1 'm~t.e-.v->
· c)Fr'lp
t" •
• J
... l
+r
---
.,..
~)G<? ,:ge-r> ·CtiwnteY?
li)PY)o Perr> f1''-o'l1W e»I.Ur} te.,r,
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11. '·
h6iode
C-19-n3 et)
fiuG~ be-cvrfl
1-fo l c:o..fho d-e.
.. ,,'n.d-o w/LA/ '
- - - - -x -fl°:j beLJ_/1"11-
. , r vJ 1'ncl.ow
I I
I 1 < I- - - ~ - . X-11<1JJ bea.mI '1 ,.., =:J
l • - e Loe.+r>o71 beam
I'<-+---~
An ode [-~&)
+
I I
C'oolaml-
c ;(
./
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12. Xusfia{ -X-'Ray Crysta{fograyfiy
1. X-ray generating equipment:
<F. { '{Cy>
_:..) / 7 ,L,,,,. 1
Q 1)pJr lr
The modern x-ray tube is a high vaccum, sealed off unit usually with a copper or
molv~denum target, although targets of chromium, iron, silver and tungsten are~sed for
. I Cv-> . , ..specia purposes. _,, "(
.)
)>( "VI -
Instrumentation: lrn s tr ti 1r1.(' n ! etlicrn hr·
J
2. In the case of x-ray fluorescence spectroscopy, crystals of known d-spacing are used
as analyzing crystals in the spectrorneter.jangel of space.'< QX- ··O-_J ~e rJJr,.,-1·
l. Solving Bragg's equation gives the d-spacing between-crystal lattice planesof atoms
that produce a constructive interference. A given unknown crystal is expected to
have many rotational planes of atoms in its structure; therefore the collection of
reflections of all the planescan be usedto(~niquelj'identifyan unknown crystal.
Application of Bragg's law:
This is Bragg'slaw.
So, nA = 2dsin9,
Or, nA = 2d sin29/ sine = 2dsin9
-- ./ 1 r
Putting all these value on equation (i)
/ ( ( c
dP / ( -·
nA = (-!!-- + -!!-- ) - 2d cos28/ sin8
smfJ sme
r!,"" l. r/i
/
r
~ /; <''{' -: fl) (_
2d - ~
So, AC' = AC cos8 = -cose = 2d cos28/ sine ·1 l'
tane
..,
-Her-e-the-patb_differ:enGe.,(AB+BC)-AC' = nA -: c
to be the same.
L"(Y!Vflh,
Now the path/dlfference between the first beam, that gets reflected along AC' and the r-ay-
second beam that gets transmittedQ'll'hen refl~cted along AB & BC respectively. -that is,
~ O· ~
(AB+BC)-AC' I ), • ' .
0
'<FJ
distance AB+BC.If two beams-are-notcontinue travelling ~9-just-mentand parallel,this extra
distance must be an integral (n) multiple of the wavelength (;)for the phasesofft~obeams ,
. I
d 2d
But, AB = BC = -:-8and AC =-8
sm tan
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13. . II'
i. Geiger counter:
The argon filled Geiger counter using halogen as a quenching gas, has a sensitive
_f. I ":>
volume.wide enough to detect nearly the entire large area beam used in some x-ray
optics. The tube is relatively insensitive to scattered hard radiation and thus its
background intensity is low. Its quantum efficiency is about 60-65% in the range,
~ I/' I Ci' .t IT I v. 1 l ', • ~
X-'Ray Crysta{Cograyfiy Kushai - %
Virtually monochromatic radiation is obtained by~eflection of x-rays fro~~rystal planes, as
governed by Bragg's equation n>-. = 2dsin0. In order to ~heemission spectrum of a
s_pe~ime.')the. analyzing crystal is mounted on _a gonii :nd rotated through the ds
OOS+gAefr anguiar re-giGR-. r'rf) r- 1'r ' Y'/(( 1 /rr&fotiO'lf'J . !,~ci~fl
(9 ll, !>ft:J')7 !.17(«
5. Detectors:
/ , -thTTU dei~ti:nr>SJ'
- I !In diffraction -studies, the Geiger~Mu!.1€'r7counter, the proportional counter and the
. 'If . d -{ J.c. _,. t"
scmtit ation counter are use to rneasure x-racranon.
3. Filters:
JJII. a./
Whenl'two spectral llnes-arel.hearly the same wavelength and.there -is>an element having
absorption edge at a wavelength between the lines, that element may be used as a filter to
reduce the11ine of shorter wavelength.
~ m-/ C t» 0 J -1 /_ c
4. Analyzing crystal.
111--11~
,.t r
Radiation from ax-raytube is collimated either by a series ofrlosely spaced, parallel metal
plates or by a bundle of tubes O.Smm in diameter or less) One collimator is placed between
/
the specimen and the analyzer crystal in a fluorescence spectrometer to limit the divergence
- •5 o.,; 151('!'? .
of the raysthat reach the crystal. The second collimator.ousuallv MUFSe-f-is placed between
the analyzer crystal and detector, where it is particularly useful at very low goniometer
angels-for preventing:;~diation/hat has not been reflected by the crystai from reaching the
detector.
Associated equipment includes high voltage generators and stabilizers. Voltage regulation is
aJe1rnctM curfl1e~
done by regulating the main A-Csupply. Current regulation is achieved by.the D-C ~-ray tube
currentand by controllingthe filament voltage. "--:> , ~ 'I rY> ,,
<
2. Collimators:
sharper diffraction. Foi fluorescence work, the focus is of much lai~er size, about 5· .i.O mm
and is viewed at a larger angel (about 20°). Since the focal sp~,'1sev~~o~ target is
~erri"'e
cooled by -the( water and is sometimes rotated when a very_.1-fls-t-a-A¬ ee;,x-raybeam is
generated. The x-ray beam» passedout of the tube through a thin window of beryllium or a
special glass. J)c_
{ ,I'
The target is ground to a slight angei so that the focal spot may be viewed from the ide. If
the focal spot is~narrow ribbon, the source appears to be very small, which lead to the
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14. Xusfia[ -X-'Ray Crysta[fograyfiy
C.,,y5/al
fo.,, l"I + obk'
'
{pfu» 0-bc .J
iii. Scintillation counter: , , L CJ u ll
.<::; 'f>[err -L'
It has a Sf:loi:tesHlead time among allA.hre , 0.25µ sec. it has nearly1-uniform and high
quantum efficiency throughout the important wavelength region 0.3-2.SA and is
usable to possibly 4A.
.j/f!ra~method:X- "~ Jdfnocbon -~s(;
(
~1. Braq's rotating crystal method: C ).flv:;;SCMnp/a cr-o-.:J.sial ~)
e.. bw~- i
In this t1ethod_A~ ')1.-ray is -~~~~rated from the }lray tube and11~ade monochromatic by
passing,~hrough;screens and-is led through the slits on the face of the crystal mounted on a
turn table which can be moved over a scale. The turn table can be rotated to give any angle
of incidence.
I
ii. Proportional counter:
The proportional counter has, about the same spectral sensitivity as the Geiger
counter; Bu~"a1ve'ry short dead1 time, about 1.5 µ sec and its response in linear to
extremely high count rates. ( 'J~o(J ~ 1,, <'ef7 ~ )
l ,-m:trcf-'~"61
from 1.5-2.lA, and decrease to 40% at 1.4-2~9-A[itsprinciple limitation lies in~ y l •':J
long dead timeo.tb~~t 270µ sec, which give-rise to counting losses at higl1'lntensities.
U ~ C -~The Geiger counter is rarely usi~ for measuring intensities in excess of about
SOOcount/sec.
%i::dThe. beam ' from the crystal passes on to a photographic plate or a recording system . - I ~'),.. I« 1,., ''
)consist~lof an ionization chamber that can move co-axially over a circular scale,
independently from the crystal and It is connected with an electrometer. The ionization
chamber contains $02 which is ionized by the reflected beam. The ionization of the gas is
directly proportional to the intensity of _1t}ex-ray.
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15. +
;
Kusha! -
2624222018
J_ I
- I' .
X-'Ray Crysta(fogra_pliy
10 14 28 30
2Theta (0)
1612
I%amorphous
3%amorphous
S% amorphous
7%amorphous
9%amorphous
10000
- 90000l1
e
::s
0
~
l;- 40000
.iii
c
.8
..5
160000
;
Oro = co 0'11 CT'1 (""'1~12 p 19 1·nf ~ .-. ·
OJ c~-·
~..~, ~,......, ,,.......
~ ....... !' ..,.
..............,t ....-~
In this method · powder is used as
t!". I
specimen inplace of large single crystal.
Powdered sample/';;l contain crystals
arranged in all possible orientations-and
@bviouslyi~~ will ..be-a.lwa.y.s ome
crystals with the proper orientation to
reinforce diffraction images from all the
atomic planes.
2. Powder-method: (!j!is01mp/.D..powtfur{t)
t, c.u'
A narrow beam of x~rayf is allowed to fall on theylfi.au powdered specimen and the
diffracted x-rays are photographed on a strip of film surrounding the substancej. On narrow
strip, thti-~ppearsas arcs arranged on each side of the bright center spot. Each pair gives
the position of a reflection of a definite order from a particular plane.Jlnd the value of -L i:..J-
glancing angel Is calculated by taking into account the distance of the arc from the center
-Lhl c1..t!'. -rvr I
spot androf the crystal from the fiim.
angel at which maximum reflection occurs is thus obtained.
( i'n+enGi!J)
electrometer. These intensities are determined for various angels of +e-f;:actien and the
ltc-li
. . ' .. - .. ' ' .. ''' ~ -
Again the current passin~ through the chamberrs proportional to the iontzatton o~gas.So r:
th f . t . .... _-f . f h . • f{ k_ hi h .'Yll"-(/()ttUd.b '
.ere,ore/ m ens:..y ot, current rs a measure o t re intensity o. x-ray w re 1s-¬ ffe-Re-Y-1 1,
14 / 20
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16. Xusfia{ -X-'Ray Crysta{Cograyhy
RPO is especially valuable for distinguishing different phases or polymorphs by their unique
diffraction pattern. Since the choice of polymorph can be important in relation to properties
such as solubility, bioavailability, and stability, the quest to produce and characterize all
accessible polvrnorphs cf a given drug substance has become an area that attracts intense
activitv. Since a new crystalline form of an API could be patented as a new pharmaceutical
pr11duct, th~ st:¥ch for every polymorph of a target compound is an invaluable step toward
C. Phase analysis and polymorph screening
Although the crystal structure of a material can be determined from a general powder
diffraction pattern, in most cases it is sufficient: simply to identify the lattice type and
dimensions of the unit cell for this new material indexing).This form of analysis is
particularly useful for characterizing alternative forms or polymorphs of registered drugs
where patents are about to expire. In addition to this technique, information such as
displacement parameters coordinates of atoms within the unit cell, site occupancy, and
preferred orientation can be obtained.
B. Crystallography and crystal structure determination
The most fundamental, yet crucially important, application of XRPD is in the identification or
fingerprinting of crystalline phases, with different crystal structures giving rise to distinct
powder diffraction patterns. The qualitative characterization of materials in this manner
finds applications in many areas, including quality control and polymorph screening.
A. R&D applications
Application of X-Ray Powder Diffraction in the Pharmaceutical Industry:
1) Nondestructive testing-in keeping with the emphasis on exploring the real-life
properties of a sample without the need to dissolve, digest, or destroy it in order to
obtain essential information.
2) Analysis of final dosage forms-allowing the integrity of the active pharmaceutical
ingredient (API) to be determine.d in the final finished product.
3) Detection of crystalline impurities-enabling the pharmaceutical scientist to detect
impurities down to 0.05%.
4) Detection of changes in morphology during production-ensuring the consistent
processing behavior of the finished product.
The advantages ofXRPD over other commonly used techniques include its
capacity for:
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17. J
The ability of XRPD to detect and quantify the presence of any polymorphic contamination,
the level of crystallographic changes, and the active ingredient in the final dosage form
allows the technique to be used to monitor and improve production efficiency and cost.
Once the active ingredient of a pharmaceutical product is in its final dosage form, the
X-'Ray Crysta{fograyfiy Kushal' -
G. Manufacturing and production:
The nondestructive nature of XRPD makes it an ideal tool for systematic drug-excipient
compatibility studies in per formulation. Careful selection of the excipients along with the
systematic evaluation of drug-exc:ipient interactions is essential to achieve consistent
release and bioavallabllity and to avoid unexpected formulation stability problems in later
stages of formulation development.
F. Compatibility studies:
In situ powder diffraction studies carried out as a function of temperature and/or relative
humidity can provide a direct means of characterizing the stability of a pharmaceutical
compound and the occurrence of hydration/dehydration processes (Figure 2}. Such non
ambient diffraction experiments can be performed at any stage of the drug development
process.
E. Stability studies:
XRPD is used successfuiiyin the determination of percent crystaiiinity (Figure1), where the
volume concentration of, for example, amorphous filler to a crystalline active matrix is
measured within a drug's dosage form. Percent crystallinity can influence a drug's
processingbehavior as well as its pharmacological performance.
D. Crystallinity determination
Figure 3 Measurement of mixtures of two azithromycin forms with different concentrations
showing a detection limit for Form II of around 0.1%.
1413 5013
Position {"2The·ta)
For1n 11 Form I
15000
· 1
1_5o/.,. Fon-nn
l.O.:Yo Form H
O.l.o/.,, Fcir-r·r) !I
tV•'' .
!
r:
'v .•/':"'..i
201JOtJ
T T
Coo..Jnts
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18. Kush.al. -X-'Ray Crysta{fograyhy
Because XRPD allows materials to be- investigated di;ectly under the conditions in which
they are used in specific applications, it is valuable for monitoring batch/dosage uniformity.
it is possible to analyze the actual percentages of individual active ingredients in the final
Josage fortr1 of a drug ln situ {figure 5), together with the percentage of any amorphous or
cryst111linP packing ingrPdit>nt.:; 11.:;Pf'L XRPO can even be used to identify and quantify the
small amounts of crystalline aerosol drug delivered by a pressurized metered dose inhaler.
For the example shown in Figure 6.. high qualitv d8ti1 were obtained v..dthC'L_!i.. anv sµecioi
sample preparation method or equiprnent.
]. Batch/dosage uniformity
302520 35
"'2Theta
15105
500
count sis
600-.,-~~~~~~~~~~~~~~~~~~~~~~~~~
nondestructive analysis, makes it useful in diverse apptications. Onesuch example is the use
cf XRPD in determining the optima! range of tableting pressure. This a!ic•>N5 ff!anuf;;.i:tun:>r5
fo t'(tAc.K -tM. {~_,l-411ll'ijll°'Phc'.c...~-huit hltta. oe;f aff..,-,':' h7 '4f'fSVILt -th0.t-tM.Jinis~f cl t"•bl.e.t-'<l.~el/-t:s
1t> tlqtt dissolu.tfq;o itJte (Figure 4j.
!. Processcontrol
XRPO is well suited for monitoring the crystal morphology of active ingredients or the
excipients (Figure 3). This is important because any change in the morphology of fillers. or in
the crystalline state of active ingredients in the final product, as a result of the
manufacturing process, can influence a drug's bioavailability. With the X'Celerator
(PANalytical), the !ewer limit of detection for minority phases has been reduced
considerably, in sorne cases even down to 0.05%.
H. Control ofingredients:
' r
arug perrorrnance.
morphology parameters measured by X-ray diffraction can be related directly to the final
17 / 20
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19. Pnod--.i. - c e-c-. I.,., :sh).L), ,J Cf )Yn~ C'Cls/..llo(n'"l'(f.
t._x~ (} 'Po."'~l f>n11dA.>e.~ -
~i<::~_.._;-v-o--h' a- e<l- <hi o~ '<2.."'-<>-Y"V"".c2' e>vv-.....c:l ~4-:'""' e e>-.,.._ lo.c!. c:io"ttR...
bQ t-1-'.s CYJL~od. .
0.
N~N~ °"""d ~""- t'lA.a .f.t'c Pri e J..vcfs.
c§~d_Q- --
0
h c.vv-. ~ cLt~no-- !- -lo"" ""'
<:ort Ro ,s; ..[Q_ f n ei .J..v(.d-
m.
l -
0
~00 - tOCJO A .
® ~ Q 0 ~ 'G °"""'-~ ~c. ti'(W L'~&
i- I s o.sg .,t (fo<:t. tt,u. fG.1"2-h'c- U t-: (2..o..~
~ Lo ti) 0..t1.Qt ~~tf' Q. n.:Q- fY'.Q_ t-(.... od. -
riv.·
s 'Y'N2~ac:l_ .,.."""o-.11t~ °"" 10..u °'W( s~o-.tt-..e.n...'~ Q- ><~
wVv.'c.-. is u.sQ_d ~tt tw ~(r f>o-rt_~'e k.s.
L. Po.-q...~clJ._ S~'t~ ~f.O~~°".,'();Y) -
4 ... "ctJsi.CJ 'Zj- X:.. 12 '() Q c, ,-""'-1., c:v..-u.- ~ O o-."' lc>J2 o.lQ cl te ~ G.~ ~
~ .§.~iJL oa-~ 'fo-~+:c..l9--~ ~...,... QQ~"""°'S, .S.Jel,-. Q~ -
(!) 2J ~ - ea v.v....-,"G fY..9._ ~d --:-
1'~ ,' .s uS-Qd ~ ~?~ ~ ;s;z.!i._ ocf ~ f>~n.._-h'~u Lo..n~
tt-.o.'Y ~ ~ '
eJ /-L cY'r •
~~G:" f'nof'~nU 'ti- IYSl.. k1
<S<fv..~ Pno P.A.~ ~~ ~-hr.I
18 / 20
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20. / '
tf"_-"-·
"":-_
.... ,. _.,, - . . .
19 / 20
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21. 20 / 20
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