physical pharmaceutics

8/12/2019 physical pharmaceutics

1/39

DV NCED PHYSIC L PH RM CEUTICS

PHYSIC L PROPERTIES OF DRUG MOLECULES

M Pharmacy 1styearDEPARTMENT OF PHARMACEUTICS

Submitted by

K.Vasanthi.


2/39


CONTENTS

1) PHYSICAL PROPERTIES OF DRUG MOLECULES.

2) DIFFERENTIAL THERMAL ANALYSIS.

3) DIFFERENTIAL SCANNING CALORIMETRY.

4) DIFFUSIVE REFLECTIVE SPECTROPHOTOMETRY.

5) X-RAY DIFFRACTION ANALYSIS.


3/39


PHYSICAL PROPERTIES OF DRUG MOLECULESThe study of these properties is essential to develop a decent formulation for a novel chemicalentity, right from the beginning to the end of drug development.

The following reasons for the evaluation of the physical properties of early developmental

candidates could be furnished:

Reducing the time and cost of introducing a molecule into the market. Selection of an appropriate form of the drug substance, such as salt form, prodrugs etc. Selection of application type (e.g.: oral, dermal, and injectable). Selection of the form of delivery (e.g.: quick acting or slow release). Increasing the ease of product development. Reducing undesirable findings during clinical phases. Release of best dug into the market.

PHYSICAL PROPERTIES:

Specific surface area, hygroscopicity, bulk density, flow properties, crystallization are the

physical properties to be investigated for new drug substances, whether flexible or stubborn.

1.Specif ic sur face area:

Surface area properties of a drug particle affect the dissolution and chemical reactivity of

a drug substance. These properties include size, shape and surface morphology of a drug

substance. The smaller the particles, the better are the bulk flow and formulation homogeneity.

The simplest way to measure the particle size is to use a microscope. However it is tedious to

measure the average particle size with such techniques. The best way is to use photomicrographs

and hemocytometer slides. Particles with a larger specific area are good absorbents for theabsorption of gases and of solutes from solution. The other factor that is also important is the

particle shape. Generally a sphere has minimum surface area per unit volume. The more

asymmetric a particle, is the greater surface area per unit volume. Since these surface propertiesaffect their homogeneity, content uniformity and dissolution properties of a tablet form, which

ultimately affect the bioavailability, these properties have to be thoroughly evaluated during

toxicological stages before clinical trials are preceded so that perfect correlation is obtained


4/39


between the bioavailability data with a formulation. When the studies are transferred from

toxicology studies to clinical studies. Accordingly, sophisticated methods are currently used.

These include adsorption methods and air permeability methods.

Quantasorb, an instrument used to obtain specific surface area measurements. A mixture

of helium and nitrogen is passed through the sample; helium is inert and is not absorbed on thepowder surface while nitrogen is absorbed on the powder. A thermal conductivity instruments

attached to the instrument measures the conductivity associated with the absorption, which inturn indicates the size of the particles.

In air permeability technique, the resistance to the flow of a fluid, such as air through aplug of compacted powder is used to determine the surface area of the powder. The greater the

surface area of the powder the greater is the resistance offered to the flow of the air.

2. Hygroscopicity:

The amount of water absorbed on the surface of drug particle influences the solid state stability

as well as the flow properties and compactibiliy of a drug substance.

Most drugs are partially hygroscopic. Hygroscopicity is one such character, provided theopportunity, the first property to be determined for a new drug characterization is to measure its

hygroscopicity. Hygroscopicity depends on the synthetic techniques and the recrystallization

methods. Judicious selection of a suitable crystal form for further development is the essentialstep in the development of solid dosage forms. The stability of a solid drug depends on the

hygroscopicity of a particular solid state of a drug, which in turn depends on the type of the

crystal or physical form of the drug that in turn depends on the synthetic techniques or the

recrystallization method for that particular drug the hygroscopicity of a substance is determinedby exposing the compound to different humidity conditions for a specific time intervals and then

assaying for water content using Karl fisher reagent etc. other methods that could be used to

measure the hygroscopicity is the gas chromatography.

Dynamic water sorption (DWS) that requires very little amount of compound for handling is alsoused in the hygroscopicity measurements at above 25c.

Hygroscopicity most of the times affects the compatibility of new drug substances. Compatibility

as a property is affected by compressibility, adhesive/cohesive interactions and mechanical

properties of the components. Water content also influences the compactibility, suggesting thathygroscopicity is one of the key issues in the development of tablet dosage forms. The

mechanism of water absorption in most of the cases is either hydrate formation or site specificadsorption. The greater the compactibility, the better are the tablet properties. Many attempts

were tried to increase the compactibility of tablet substance. In this regard the reduction of

hygroscopicity of drug substance is very crucial. This can be achieved by obtaining drug crystals

by using altered synthesis or recrystallization techniques.


5/39


3.Bulk density and porosity:

Bulk density is an essential pharmaceutical property to be thoroughly investigated for a newchemical entity .this is because of its important in capsule filling and tablet compression.

Apparatus high bulk density will not allow a capsule to be filled in the specific volume and in

addition during tablet compression, the tablets would not be compressed either because of therebounded effect or because of the bulk volume occupied by the tablet powder in the die. Bulk

density along with flow properties of a drug substance occupied major investigation problems,

which have to be sorted out as early as possible in new drug chemical entity investigations.

Experimentally, the true density is determined by suspending drug particles in solvents of

various densities and in which the compound is insoluble. In these measurements, wetting and

pore penetration are enhanced by the addition of a small quantity of surfactant to the solventmixtures. After vigorous shaking, the sample are centrifuged briefly and then lift to stand

undisturbed until flocculation or settling has reached equilibrium the sample that retains

suspended corresponds to the true density of the material. One way of avoiding this densityproblem for a new chemical entity is to use wet granulation and then punch the tablet or fill the

granules in a capsule. If a drug has very high bulk density, it may not be used in a direct

compression process. The drug has to be modified so as to obtain bulk drug with good

compressibility properties. In modern solid dosage form technology, the current practice is toprepare dosage forms with reduced excipient content. Technology that reduces the size of the

dosage form, improve the compressibility of the solid drug, its flowability and enhances the

aesthetics as desirable.

4.Crystall ization:

Crystallization is a common phenomenon in pharmaceutical processing right from the

manufacturing of active pharmaceutical ingredient to the storage of final formulation approved.

Crystallization process can be termed as a Meta stable thermo dynamic state. This occurs

because any substance or events tend to stabilize to reach the lowest possible thermodynamic

state. This state of any substance is termed as a metastable state. This metastable state is either

intentionally or unintentionally created either by supersaturating, in the crystallization of desired

solid state modifications and in the control of solid phase conventions during isolation,

manufacturing, storage and dissolution. Examples of metastable state include solid solutions,

freeze concentrated solutions, solutions of weak acids/bases exposed to a PH changes, solutions

prepared by dissolving a solid state modification with a higher solubility, residual solutionsduring filtration, granulation and drying. The factors that can appear in the affect crystallizationinclude molecular or ionic transport, viscosity, super saturation, solubility, solid liquid interfacial

tension and temperature. Nuclear kinetics is experimentally, determined from measurement of

nucleation rates, induction time and metastability zone width as a function of initialsupersaturation. Currently, molecular simulations from the data obtained from the solution and

crystal structure of drug substance is used in establishing the crystal structure of new chemical


6/39


entity. Molecular association process in super saturated systems is obtained by laser Raman

spectroscopy and laser light scattering is used in the identification of pre-nucleation clusters and

growth units well defined experimental conditions. Raman fluorescence spectroscopic technique

used is capable of providing information about the solution structures are the species present in

the solutions.

PHYSICO CHEM ICAL PROPERTIES :

Several physic-chemical properties of new leads have to be investigated very early onthese could include Pka , solubility analysis, partition co-efficient, dissolution rate , solid state

stability , solution state stability.

1.Pka:-

Pka determination is important because this controls solubility and consequently the oral

absorption of a molecule in a given solution, formulation or body fluids. In ph. range from 1-10,the solubility and consequently oral absorption could be altered by orders of magnitude with

changing ph. Pka is the ph. at which 50% of the substance is ionized. Buffer, temperature, ionic

strength and cosolvents effect the pka values. Incorporation of cosolvents in pka measurementsinstrument methods is important because of the likely poor solubility and possible precipitation

of these compounds in aqueous media.

Potentiometric and spectrophotometric methods are the popular methods used in the

determination of pka of new chemical entity. Currently, glpka instrument is in the market for the

determination of pka of new chemical entities. The instrument measures the potentiometric pka

of a compound. The advantage offered by the current glpka instrument is that, the assays are

fully automated; temperatures and ionic strength are monitored during the runs and four line

cosolvents options available. The advantage is that using organic solvents help in determinationionization constants of poorly soluble compounds.

As per indications of manufacturers, the functions of the instruments include:

Pkas is measured from 2 to 12. Log p measurements from -2 to +8. Overlapping and multiple pkas routinely measured. Easily handles protogenic counter ions. Sparingly soluble compounds titrated in either possible supported cosolvents. Typical sample concentrations of 0.25 to 0.5 m M( 1 2 mg of 400 MW compounds in

10ml).

Fast ( typical titration = 25mins). Accurate and precise.


7/39


In spectrophotometric method of determination, at a given PH, if the ion concentrations

are determined using beers law one can calculate the approximate pka of a drug. For example, if

the drug is a free acid [HA] in equilibrium with its base[A], then

Pka = PH + log [HA] / [A]

When [HA] = [A], as determined by their respective absorbence in thespectrophotometric determinations, pka = PH.

2.Solubi li ty analysis:

Solubility analysis is essential for further processing of a compound. The factors that would

effect the solubility of a new chemical entity are PH, temperature, ionic strength and buffer

concentrations. For equilibrium solubility determinations, different methods are employed.

To determine the aqueous solubility, the drug is solubilized in which it is highly soluble and this

solution is slowly added to the distilled water and agitated. At the end of agitation, thesuspension is filtered to obtain a filtrate that is then assayed using techniques like

spectrophotometry and HPLC. Usually, the solubility of drugs is more in high temperature

conditions. The principle can be used to saturate the aqueous suspension containing a drug. Thecompound that is not soluble is precipitated out. This is filtered and submitted for analysis to

determine the solubility of a drug substance. The simplest technique that is routinely used to add

excess of drug to water and this is then agitated overnight to obtain maximum solubility of thedrug in the media and then filtered and assayed to obtain the desired aqueous solubility.

To determine the solubility of a poorly soluble compound in water, generally 24hrs equilibrium

time is given. During the time the drug slowly dissolves in water. It is a similar phenomenonwith the dissolution of the drug in gastric fluid or dissolution media from a solid powder or a

capsule or from a tablet dosage form. The drug is slowly dissolved and the drug dispersed by

agitation to form a uniform solution. It is then analyzed to obtain the concentration of the drug in

the dissolution medium. Drugs with limited solubility (< 1%) in the fluids of gastro intestinal

tract often exhibit poor or erratic absorption unless dosage forms are specifically tailored for thedrug.

3.Parti tion coeffi cient:

Octanolwater partition coefficient is the ratio of concentration of a chemical in Octanol and inwater at equilibrium and at a specified temperature. Octanol is an organic solvent that is used as

a surrogate for natural organic matter. The Octanol water partition coefficient has beencorrelated to water solubility; therefore the water solubility of a substance can be used to

estimate Octanolwater partition coefficient.


8/39


The Octanol water partition coefficient ( Kow) is defined as the ratio of chemicals

concentration in the Octanol phase to its concentration in the aqueous phase of a two phase

Octanolwater system.

K ow = Concentration in Octanol phase / Concentration in aqueous phase.(I1)

Values of K oware thus unit less. The parameter is measured using low solute concentrations,values of Koware usually measured at room temperature ( 20 - 25c). The effect of temperature

on K owis not great. Usually on the order of 0.0010.01 log Kow/ c and may be either + or ve.

The octanol / water partition coefficient is not the same as the ratio of the chemicals solubility in

octanol to its solubility in water, because organic and aqueous phases of the binary octanol /

water system are not pure octanol and pure water. Kowis often found to be a function of solute

concentration. The chemical in question is added to a mixture of octanol and water whose

volume ratio is adjusted according to the expected value of Kow. Very pure octanol and water

must be used, the concentration of the solute in the system should be less than 0.01 mole / litre.The system is shaken gently until equilibrium was achieved (15mins 1hr). centrigugation isgenerally required to separate the two phases, especially if an emulsion is formed. An

appropriate analytical technique is then used to determine the solute concentration to each phase.

A rapid laboratory estimate of Kowmay be obtained by measuring the retention time in HPLC ,the logarithm or retention time and the logarithm of Kow have been found to be linearly

correlated. Conversely chemicals with high Kow(>104) are very hydrophobic.

4.Dissolution rate :

Dissolution rate is the predictable measure of time required for a given dug or active ingredient

in an oral solid dosage form to go into solution under the specified set of conditions. Sinceabsorption and physiological availability of any nutritional supplement is largely dependent upon

having in a dissolved state, a suitable dissolution rate is crucial. Calculating intrinsic dissolution

rate makes comparison of the individual drug substances and the effect of different conditions on

drug dissolution. The intrinsic dissolution rate is generally defined as the dissolution rate of a

pure drug substance under the conditions of constant surface area.

Intrinsic dissolution is generally determined by measuring the dissolution of a non-disintegrating

disc made by compressing pure powder drug substance under high pressure using a specially

constructed punch and die system. The test material is compressed with a bench top punchtablet press for 1 minute at the minimum compression pressure necessary to form a non-

disintegrating compacted tablet. Changes in the crystal form may occur during compression,

conformation of the solid form should be verified by powder x ray diffraction technique.

Compression plays an important role in the test, if it is too low, a non-disintegrating tablet maynot be obtained and if its too high it may change the crystal form. It is important to study the

effect of compression pressure on intrinsic dissolution rates as it has been observed for several

drug substances that the intrinsic dissolution rate varies with compression pressure.


9/39


Dissolution rate determines the availability of the drug for absorption when slower than the

absorption, dissolution becomes the rate limiting step. Overall selection of an appropriate

formulation can control absorption. Dissolution rate is affected by whether the drug is in salt,

crystal or hydrated form. The sodium salt of weak acids ( ex: barbiturates, salicylates ) dissolve

faster than their corresponding free acids regardless of the PH of the medium.

5. Soli d state stabil ity:

This involves stability of the drug substance as a solid and stability of a drug substancein a solid dosage form. Drug instability in pharmaceutical formulation may be detected in some

instances by a change in the physical appearance, color, odor, taste or texture of the formulation

whereas the chemical stability of the drug substance is determined by chemical analysis. The

second study is termed reaction kinetics.

A kinetic study on a drug substance is examined by subjecting an NCE in several

physical and chemical and stressed conditions. The samples are withdrawn at periodic times andassayed for the drug content using a HPLC or other techniques. Then the active chemicals and

degrades are mathematically dissected to obtain chemical kinetics of the drug substance. This

reaction kinetics could be zero order, first order, second order and sometimes inverse reaction

kinetics. Inverse kinetics are determined when there is a transition of one impurity to other or

one degrading to the drug, which may help in long run in the formulation movement predictions

and during storage. As a standard stability protocol, the utilization of exaggerated conditions

such and high temperature and high light intensity and high humidity are investigated for the

stability determination. Accelerated temperature studies, for example, may be conducted for 6

months at 40c and 75% RH. If a significant change occurs in the drug or drug product under

these conditions, lesser temperature and humidity may be used such as 30c and 60% RH.Product container, closures, and other packaging conditions features are also to be considered in

stability testing during this stage.

6.Solution state stabil ity:

Solution state stability of a drug is valid for stability testing of liquid formulations and for HPLCmethod development. NCE is generally mixed in aqueous media at different PH conditions. The

samples are withdrawn at regular time intervals and are submitted for analysis. Once the data is

obtained, the active amount present is mathematically fitted to obtain the reaction kinetics in the

solution state. Different PH conditions, different humidity conditions, different temperatureconditions, different packaging conditions can be used in the solution state stability

determination. The reaction kinetics is the same and is zero order, first order, second order, multi

order and inverse kinetics. In solid state characterization apart from the stability impurity,polymorphs, racemates etc are determined as a first step in the physical characterization of a new

chemical entity.


10/39


7.Enantiomers and racemates:

Enantiomer is one of two stereoisomers that aremirror images of each other that are non-superimposable (not identical), much as one's left and righthands are the same except for

opposite orientation. Organic compounds that contain an asymmetric (chiral) Carbon usually

have two non-superimposable structures. These two structures are mirror images of each otherand are, thus, commonly called enantiomorphs Hence, optical isomerism is now commonly

referred to as Enantiomerism.

Enantiomers have, when present in a symmetric environment, identical chemical and physical

properties except for their ability to rotate plane-polarized light (+/) by equal amounts but in

opposite directions (although the polarized light can be considered an asymmetric medium). Amixture of equal parts of an optically active isomer and its enantiomer is termedracemic and has

zero net rotation of plane-polarized lightbecause the positive rotation of each (+) form is exactly

counteracted by the negative rotation of a () one.

Enantiomers of each other often show different chemical reactions with other substancesthat are also enantiomers. Since many molecules in the body of living beings are enantiomers

themselves, there is often a marked difference in the effects of two enantiomers on living beings.

Indrugs, for example, often only one of a drug's enantiomers is responsible for the desired

physiologic effects, while the other enantiomer is less active, inactive, or sometimes even

responsible foradverse effects (unwanted side-effects).

The following table lists pharmaceuticals that have been available in bothracemic and single-

enantiomer form.

Racemic mixture Single-enantiomer

Amphetamine (Benzedrine) dextroamphetamine (Dexedrine)

Bupivacaine (Marcain) levobupivacaine (Chirocaine)

Cetirizine (Zyrtec /Reactine)

levocetirizine (Xyzal)
http://en.wikipedia.org/wiki/Stereoisomerhttp://en.wikipedia.org/wiki/Mirror_imagehttp://en.wikipedia.org/wiki/Chirality_(chemistry)http://en.wikipedia.org/wiki/Plane_(mathematics)http://en.wikipedia.org/wiki/Polarized_lighthttp://en.wikipedia.org/wiki/Racemichttp://en.wikipedia.org/wiki/Polarized_lighthttp://en.wikipedia.org/wiki/Pharmaceutical_drughttp://en.wikipedia.org/wiki/Adverse_effectshttp://en.wikipedia.org/wiki/Racemichttp://en.wikipedia.org/wiki/Enantiomerhttp://en.wikipedia.org/wiki/Amphetaminehttp://en.wikipedia.org/wiki/Benzedrinehttp://en.wikipedia.org/wiki/Dextroamphetaminehttp://en.wikipedia.org/wiki/Bupivacainehttp://en.wikipedia.org/wiki/Levobupivacainehttp://en.wikipedia.org/wiki/Cetirizinehttp://en.wikipedia.org/wiki/Levocetirizinehttp://en.wikipedia.org/wiki/Levocetirizinehttp://en.wikipedia.org/wiki/Cetirizinehttp://en.wikipedia.org/wiki/Levobupivacainehttp://en.wikipedia.org/wiki/Bupivacainehttp://en.wikipedia.org/wiki/Dextroamphetaminehttp://en.wikipedia.org/wiki/Benzedrinehttp://en.wikipedia.org/wiki/Amphetaminehttp://en.wikipedia.org/wiki/Enantiomerhttp://en.wikipedia.org/wiki/Racemichttp://en.wikipedia.org/wiki/Adverse_effectshttp://en.wikipedia.org/wiki/Pharmaceutical_drughttp://en.wikipedia.org/wiki/Polarized_lighthttp://en.wikipedia.org/wiki/Racemichttp://en.wikipedia.org/wiki/Polarized_lighthttp://en.wikipedia.org/wiki/Plane_(mathematics)http://en.wikipedia.org/wiki/Chirality_(chemistry)http://en.wikipedia.org/wiki/Mirror_imagehttp://en.wikipedia.org/wiki/Stereoisomer


11/39


8.Impurities:

Impurities in new drug substances are addressed from two perspectives:

Chemistry aspects include classification and identification of impurities, reportgeneration, listing of impurities in specifications, and a brief discussion of analyticalprocedures.

Safety aspects include specific guidance for qualifying those impurities that were notpresent, or were present at substantially lower levels, in batches of a new drug substance

used in safety and clinical studies.

The studies conducted to characterize the structure of actual impurities present in a new drugsubstance at a level greater than 1% the identification threshold many batch manufactured by the

proposed commercial process should be identified. In addition, any degradation product

observed in stability studies at recommended storage conditions at a level greater than 1% theidentification threshold should be identified. Identification of impurities present at apparent level

of not more than 1% the identification threshold is generally not considered necessary.

9.Polymorphs:

Polymorphism is often characterized as the ability of a drug substance to exist as two or more

crystalline phases that have different arrangements and or conformations of the molecules in the

crystal lattice. Amorphous solids consist of disordered arrangements of molecules and do not

possess a distinguishable crystal lattice. Solvates are crystalline solid adducts containing either

stoichiometric or nonstoichiometric amounts of a solvent incorporated within the crystalstructure. If the incorporated solvent is water, the solvates are also commonly known ashydrates.polymorphism refers to the occurrence of different crystalline forms of the same drug

substance.

Polymorphs and solvates of a pharmaceutical solid can have differen chemical and physical

properties such as melting point, chemical reactivity, apparent solubility, dissolution rate, opticaland electrical properties,vapour pressure, and density. The properties can have a direct impact on

the processability of drug substances and the quality / performance of drug products, such as

stability, dissolution, and bioavailability. A metastable pharmaceutical solid form can change

crystalline structure or solvate / desolvate in response to changes in environmental conditions,processing, or over time.


12/39


13/39


DIFFERENTIAL THERMAL ANALYSIS

DTA measures the temperature difference between the sample and a reference as a function of

Temperature or time when heating at a constant rate.

PRINCIPLE

Differential thermal analysis(or DTA) is a thermo analytic technique, similar todifferential

scanning calorimeter. In DTA, the material under study and an inert reference are made to

undergo identical thermal cycles, while recording any temperature difference between sample

and reference. This differential temperature is then plotted against time, or against temperature

(DTA curve orthermogram). Changes in the sample, either exothermic or endothermic, can be

detected relative to the inert reference. Thus, a DTA curve provides data on the transformations

that have occurred, such as glass transitions, crystallization, melting and sublimation. The area

under a DTA peak is the enthalpy change and is not affected by the heat capacity of the sample.

INSTRUMENTATION

A DTA consists of a sample holder comprising thermocouples, sample containers and a

ceramic or metallic block; a furnace; a temperature programmer; and a recording system. The

key feature is the existence of two thermocouples connected to a voltmeter. One thermocouple isplaced in an inert material such asAl2O3,while the other is placed in a sample of the material

under study. As the temperature is increased, there will be a brief deflection of the voltmeter if

the sample is undergoing a phase transition. This occurs because the input of heat will raise the

temperature of the inert substance, but be incorporated as latent heat in the material changing

phase.
http://en.wikipedia.org/wiki/Thermal_analysishttp://en.wikipedia.org/wiki/Differential_scanning_calorimetryhttp://en.wikipedia.org/wiki/Differential_scanning_calorimetryhttp://en.wikipedia.org/wiki/Thermogramhttp://en.wikipedia.org/wiki/Aluminium_oxidehttp://en.wikipedia.org/wiki/Aluminium_oxidehttp://en.wikipedia.org/wiki/Aluminium_oxidehttp://en.wikipedia.org/wiki/Aluminium_oxidehttp://en.wikipedia.org/wiki/Aluminium_oxidehttp://en.wikipedia.org/wiki/Aluminium_oxidehttp://en.wikipedia.org/wiki/Thermogramhttp://en.wikipedia.org/wiki/Differential_scanning_calorimetryhttp://en.wikipedia.org/wiki/Differential_scanning_calorimetryhttp://en.wikipedia.org/wiki/Thermal_analysis


14/39


Instrumentation and working

The sample is loaded into a crucible, which is then inserted into the sample well (markedS). A reference sample is made by placing a similar quantity of inert material (such asAl2O3) in a second crucible.

This crucible is inserted in the reference well, marked R. The dimensions of the twocrucibles and of the cell wells are as nearly identical as possible; furthermore, the weights

of the sample and the reference should be virtually equal. The sample and reference should be matched thermally and arranged symmetrically with

the furnace so that they are both heated or cooled in an identical manner. The metal block surrounding the wells acts as a heat sink. The temperature of the heat

sink is slowly increased using an internal heater. The sink in turn simultaneously heats

the sample and reference material. A pair of matched thermocouples is used. One pair is in contact with the sample or the

sample container; the other pair is in contact with the reference. The output of thedifferential thermocouple, Ts - Tr or DT, is amplified and sent to the data acquisition


15/39


system. This allows the difference in temperature between the sample and the reference

to be recorded as a function of the sample temperature, the reference temperature or time. If there is no difference in temperature, no signal is generated, even though the actual

temperatures of the sample and reference are both increasing. Operating temperatures for DTA instruments are generally room temperature to about

1600 OC; some DTA equipmentsare capable of operating from -150 OC to 2400 OC.To reach the very low sub-ambient temperatures, a liquid nitrogen cooling accessory is

needed. Some low temperatures (but, not -150 OC) may be reached with electrical

cooling devices or with forced air-cooling. When a physical change takes place in the sample, heat is absorbed or generated. For

example, when a metal carbonate decomposes, CO2 is evolved. This is an endothermic

reaction; heat is absorbed and the sample temperature decreases. The sample is now at a

lower temperature than the reference. The temperature difference between the sample and

reference generates a net signal, which is recorded.

Modern DTA instruments have the ability to change atmospheres from inert to reactivegases, as is done in TGA. As is the case with TGA, the appearance of the DTA thermal

curve depends on the particle size of the sample, sample packing, the heating rate, flowcharacteristics inside the furnace, and other factors.

Thermal matching between the sample and the reference is often improved by dilutingthe sample with the inert reference, keeping the total masses in each crucible as close toeach other as possible.

Sample crucibles are generally metallic (Al, Pt.) or ceramic (silica) and may or may nothave a lid. Many metal pans with lids have the lid crimped on using a special tool.

Best results are obtained when the area of contact between the sample and the pan orcrucible is maximized.

Samples are generally in the 110 mg range for analytical applications.APPLICATIONS

DTA is widely used in the pharmaceutical and food industries.

DTA may be used in cement chemistry, mineralogical research and in environmental studies.DTA curves may also be used to date bone remains or to study archaeological materials.

Composition of Multicomponent Systems Thermal Stability of Materials Oxidative Stability of Materials Estimated Lifetime of a Product Decomposition Kinetics of Materials The Effect of Reactive or Corrosive Atmospheres on Materials Moisture and Volatiles Content of Materials. To construct phase diagrams and study phase transitions.


16/39


To fingerprint substances. To determine M.Pt. ,B.Pt., decomposition temperatures of organic compounds. To characterize inorganic materials. To quantitatively analyze polymer mixtures.

To characterize polymers.


17/39


18/39


Differential scanning calorimetry is a technique we use to study what happens topolymers when they're heated.

We use it to study what we call the thermal transitions of a polymer.Heat capacity

We can learn a lot from this plot. Let's imagine we're heating a polymer. When we start heating

our two pans, the computer will plot the difference in heat output of the two heaters againsttemperature. That is to say, we're plotting the heat absorbed by the polymer against temperature.

The plot will look something like this at first.

The heat flow at a given temperature can tell us something. The heat flow is going to be shownin units of heat, q supplied per unit time, t. The heating rate is temperature increase T per unit

time, t.

Temperature will go up by a certain amount, and the amount of heat it takes to get a certaintemperature increase is called the heat capacity, or Cp. We get the heat capacity by dividing the

heat supplied by the resulting temperature increases.

The glass transition temperature

Of course, we can learn a lot more than just a polymer's heat capacity with DSC. when we heat

the polymer a little more after a certain temperature, our plot will shift upward suddenly, like this


19/39


20/39


Melting

If we keep heating our polymer past its Tc, eventually we'll reach another thermal transition, one

called melting. When we reach the polymer's melting temperature, or Tm, those polymer crystals

begin to fall apart, that is they melt. The chains come out of their ordered arrangements, and

begin to move around freely. When the polymer crystals melt, they must absorb heat in order todo so. Melting is a first order transition. This means that when the melting temperature reaches,

the polymer's temperature won't rise until all the crystals have melted. This means that the little

heater under the sample pan is going to have to put a lot of heat into the polymer in order to both

melt the crystals and keep the temperature rising at the same rate as that of the reference pan.This extra heat flow during melting shows up as a big peak on our DSC plot, like this

So let's review now: we saw a step in the plot when the polymer was heated past its glasstransition temperature. Then we saw a big dip when the polymer reached its crystallization

temperature. Then finally we saw a big peak when the polymer reached its melting temperature.

To put them all together, a whole plot will often look something like this:

Of course, not everything you see here will be on every DSC plot. The crystallization dip and the

melting peak will only show up for polymers that can form crystals. Completely amorphouspolymers won't show any crystallization, or any melting either. But polymers with both

crystalline and amorphous domains will show all the features you see above.

Putting it all together

Then we saw a big dip when the polymer reached its crystallization temperature. Then finally we

saw a big peak when the polymer reached its melting temperature. To put them all together, awhole plot will often look something like this then we saw a big dip when the polymer reached

its crystallization temperature. Then finally we saw a big peak when the polymer reached its

melting temperature. To put them all together, a whole plot will often look something like this


21/39


If you look at the DSC plot you can see a big difference between the glass transition and the

other two thermal transitions, crystallization and melting. For the glass transition, there is no dip,

and there's no peak, either. This is because there is no latent heat given off, or absorbed, by the

polymer during the glass transition. Both melting and crystallization involve giving off or

absorbing heat. The only thing we do see at the glass transition temperature is a change in the

heat capacity of the polymer.Because there is a change in heat capacity, but there is no latent heat involved with the glass

transition, we call the glass transition a second order transition. Transitions like melting and

crystallization, which do have latent heats, are calledfirst order transitions.

I NSTRUMENTATION AND WORKING

The calorimeter consists of a sample holder and a reference holder. Both are constructed of

platinum to allow high temperature operation. Under each holder is a resistance heater and a

temperature sensor. Currents are applied to the two heaters to increase the temperature at theselected rate. The difference in the power to the two holders, necessary to maintain the holders at

the same temperature, is used to calculate dH/dt. A schematic diagram of a DSC is shown inFigure 1. A flow of nitrogen gas is maintained over the samples to create a reproducible and dry

atmosphere. The nitrogen atmosphere also eliminates air oxidation of the samples at high

temperatures. The sample is sealed into a small aluminum pan. The reference is usually an empty

pan and cover. The pans hold up to about 10 mg of material.


22/39


Figure 1.Schematic of a DSC.

The triangles are amplifiers that determine the difference in the two input signals. The sample

heater power is adjusted to keep the sample and reference at the same temperature during the

scan.

Figure 2. Typical DSC scan.

The heat capacity of the sample is calculated from the shift in the baseline at the startingtransient. Glass transitions cause a baseline shift.


23/39


Crystallization is a typical exothermic process and melting a typical endothermic process, trH

is calculated from the area under the peaks.

During the heating of a sample, for example, from room temperature to its decomposition

Temperature, peaks with positive and negative dH/dt may be recorded; each peak corresponds

To a heat effect associated with a specific process, such as crystallization or melting (Fig. 2).

A special case in which the temperature of a phase transformation is of great importance inPolymers are the glass transition temperature, Tg.

In the DSC experiment, Tg is manifested by a drastic change in the base line, indicating a change

in the heat capacity of the polymer.

No enthalpy is associated with such transition (for which reason it is also called a second ordertransition); therefore, the effect in a DSC curve is slight and is observable only if the instrument

is sensitive enough.

The heat flow may be measured as exothermic or endothermic and plotted against temperature.

The slope of the curve is the rate of change of heat capacity Cp/dt.

During the heating of a sample, for example, from room temperature to its decomposition

temperature, peaks with positive and negative dH/dt may be recorded; each peak corresponds

to a heat effect associated with a specific process, such as crystallization or melting.

The temperature scan rate is

Scan rate = DT/dt

Using the chain rule

Where dH/dt is the shift in the baseline of the thermogram and the last derivative is just the

inverse of the scan rate. For differential measurements, we determine the difference in the heatcapacity of the sample and the reference.

The units of the heat flow are mcal sec-1 and the temperature scan rate is usually expressed as

Cmin-1. So to be consistent with units you must multiply by 60 sec min-1


24/39


APPLICATIONS

Differential scanning calorimetry can be used to measure a number of characteristicproperties of a sample.

Using this technique it is possible to observe fusion and crystallization events as well asglass transition temperatures Tg.

DSC can also be used to study oxidation, as well as other chemical reactions. Glasstransitions may occur as the temperature of an amorphous solid is increased. These

transitions appear as a step in the baseline of the recorded DSC signal. This is due to thesample undergoing a change in heat capacity; no formal phase change occurs.

The technique is widely used across a range of applications, both as a routine quality testand as a research tool. The equipment is easy to calibrate, using low melting indium at

156.5985 C for example, and is a rapid and reliable method of thermal analysis.

Polymers DSC is used widely for examining polymeric materials to determine their thermal

transitions. The observed thermal transitions can be utilized to compare materials . Composition of unknown materials may be completed using a technique such as IR. Melting points and glass transition temperatures for most polymers are available from

standard compilations, and the method can show polymer degradation by the lowering of

the expected melting point, Tm. The percent Crystalline content of a polymer can be estimated from the

crystallization/melting peaks of the DSC graph .

DSC can also be used to study thermal degradation of polymers using an approach. Impurities in polymers can be determined by examining thermo grams for anomalous

peaks, and plasticizers can be detected at their characteristic boiling points.

Liquid crystals DSC is used in the study of liquid crystals. Using DSC, it is possible to observe the small energy changes that occur as matter

transitions from a solid to a liquid crystal and from a liquid crystal to an isotropic liquid.

Oxidative stability Using differential scanning calorimetry to study the stability to oxidation of samples

generally requires an airtight sample chamber.

Such analysis can be used to determine the stability and optimum storage conditions for amaterial or compound.

Safety screening DSC makes a reasonable initial safety screening tool. The presence of an exothermic event can then be used to assess the stability of a

substance to heat.

A much more accurate data set can be obtained from an adiabatic calorimeter, but such atest may take 23 days from ambient at a rate of a 3 C increment per half hour.


25/39


Drug analysis

DSC is widely used in the pharmaceutical and polymer industries. For the polymer chemist, DSC is a handy tool for studying curing processes, which

allows the fine tuning of polymer properties.

In the pharmaceutical industry it is necessary to have well-characterized drug compoundsin order to define processing parameters.

If it is necessary to deliver a drug in the amorphous form, it is desirable to process thedrug at temperatures below those at which crystallization can occur.

General chemical analysis Freezing-point depression can be used as a purity analysis tool when analyzed by

differential scanning calorimetry.

Consequently, less pure compounds will exhibit a broadened melting peak that begins atlower temperature than a pure compound.


26/39


DIFFUSIVE REFLECTIVE SPECTROPHOTOMETRY

PRINCIPLE

A beam of light impinging on a flat polished surface of a crystal larger than the beamCross section is partly specularly reflected and partly refracted following the laws of geometric

optics (contained in the Fresnel equations). In absorbing materials, the radiant flux Is absorbed

according to the well-known Lambert Absorption Law.

I = I e-K xEq. [1]

Where I is the radiation flux transmitted from an initial flux I0 following passage through a

Layer of thickness x of a medium with an absorption (or extinction) coefficient KT measuredIn transmission.

When the dimensions of the particle are small compared with the beam cross section but largerelative to the light wavelength, diffraction phenomena also occur because rays striking the

crystal and passing by it result in interferences among elementary waves. In powders of

randomly oriented particles of such size, part of the incident light goes back at all angles into the

hemisphere of provenance of the light. The phenomenon resulting from the reflection, refraction,diffraction, and absorption by particles oriented in all directions is called diffuse (or volume)

reflection, in contrast with regular (or directional) reflectionfrom a plane phase boundary. For ideal diffuse reflection, the angular distribution of reflectedlight is independent of the angle of incidence and obeys the Lambert Cosine Law.

This law states that the remitted radiation per unit surface and unit solid angle is proportional

to the cosine of the angle i of incident light and the cosine of the angle of observation, e. There is

no such thing as an ideal diffuse reflector, but near-Lambertian behavior is normally observed intightly pressed powder samples. If the dimensions of the particle are similar to, or smaller than,

the wavelength, then the contributions of reflection, refraction, and diffraction to the intensity

and angular distribution of the remitted radiation flux are comparable and impossible to separate.

The phenomenon is then designated as scattering.

Various theories have provided a reasonably solid basis to interpret single scattering by isolated

molecules of absorbing or non absorbing isotropic particles. However, as the distance between

particles decreases, single scattering gives way to multiple scattering, which logically

predominates in densely packed crystal powders and pigment mixtures.

There is no general quantitative solution to the problem of multiple scattering. Purely

phenomenological theories have thus been developed to describe the system properties. Several


27/39


theories are based on two constants that characterize the absorption and scattering per unit layer

thickness of the medium. These so-called coefficients of absorption and scattering are generally

taken to be properties of the irradiated layer, assumed to be a continuum, and are experimentally

accessible.

THE KUBELKAMUNK THEORY

The Kubelka-Munk theory predicts a linear relationship between spectral intensity and sample

concentration under conditions of constant scattering coefficient and infinite sample dilution in a

non absorbing matrix.

The Kubelka and Munk (1931) theory assumes that a plane-parallel layer of thickness X capable

of both scattering and absorbing radiation is irradiated in the x direction with a diffuse

monochromatic radiation flux I. The layer is very extensive relative to X and can be split intoinfinitesimal layers of thickness dx. The diffuse radiation flux in the negative and positive x

directions are designated I and J, respectively. If, in passing through dx, the downward flux I isdecreased by an amount KIdx by absorption, and increased by an amount SIdx by scattering, and

a similar reasoning is made for the upward flux J, then the following differential equations can

be derived

Eq. [2,3]

where K and S are the absorption and scattering coefficient of the sample, respectively.

The most general solution is

Eq. [4]

Where R is the reflectance of the layer over a background of reflectance Rg, cothbSX the

Hyperbolic cotangent of bSX, X the layer thickness, a = 1 + K/S, and b = (a2 1)0.5.

furtherincrease in thickness will fail to change the reflectance. Under these conditions, the

Reflectance is given by R and Eq. [4] yields


28/39


29/39


INSTRUMENTATION

Diffuse reflectance measurements are usually made by using a UV-visiblespectrophotometer equipped with a diffuse reflectance accessory capable of collecting the

reflected flux.

Currently, many high -performance, research spectrophotometers can be fitted with anintegrating sphere/detector module, which usually replaces the cell holders used for

transmission measurements in the measuring compartment.

An integrating sphere is essentially a hollow sphere internally coated with a whitematerial of diffuse reflectance close to 1.

The sphere has apertures through which a beam of radiant energy can penetrate and portsfor mounting samples and standards and placing the appropriate detectors.

Commercially available spheres range from 50 to 250 mm in diameter and are internallycoated with highly diffusing poly tetrafluoroethylene (PTFE) or barium sulfate (BaSO4).

Reflectance measurements are performed under specific geometric conditions. Reflectance is measured by illuminating the sample with diffuse light the angle between

the normal to the sample surface and the axis of the viewing beam not exceeding 10.

Most commercial spectrophotometers measure directionalhemispherical reflectance,whereby the sample is illuminated by a beam whose axis does not depart by more than

10 from the normal to the sample and the reflected radiation collected by the sphere goes

to the detector.

Integrating spheres usually contain small baffles placed between the sample and the areaof the sphere that is illuminated or viewed.

These baffles prevent directly reflected light from superimposing on the illuminatedsample or on the area of the surface that is being viewed.

SAMPLE PREPARATION

Diffuse reflectance spectra are significantly sensitive to the manner in which the soil ormineral mixture sample is prepared.

The operator must thus carefully consider the factors potentially influencing thoseFeatures of the spectrum from which useful information is to be derived.

Particle size is the factor most strongly affecting reflectance, as shown by theoccasionally dramatic changes in soil color upon grinding.

The best results are obtained with small particle sizes, so it is generally advisable to grindthe sample to a fine silt (


30/39


Consistent results and preservation of the spectral features of interest can be achieved inmost instances simply by grinding the sample in an agate mortar, so that minerals are in

the volume-scattering region.

Preferential orientation of particles of layer silicates and occasionally other minerals mustbe avoided because it results in regular reflection, thus breaking the laws of diffuse

reflection. Dilution of the sample with a barium sulfate standard usually reduces preferential

orientation to an acceptable minimum.

Moist soil samples have occasionally been used, in observing color changes uponmoistening.

Moisture loss during measurement, which can be a major source of error, must beevaluated by measuring the sample spectrum at variable intervals.

SAMPLE HOLDERS

Many holders possess a cover glass to prevent loose powder from falling into, anddamaging, the integrating sphere when sample ports are vertical or horizontallypositioned on top of the sphere.

The only choice available with vertical ports is to use self-supporting pressed powdermounts.

Rectangular or ovulated holes with a maximum size of 8 to 10 by 12 to 16 mm areusually suitable.

Portable spectrophotometers allow the rapid measurement of the reflectance of unalteredsoil surfaces or ground soil samples without the need for special preparation.

However, they generally measure reflectance at relatively large wavelength steps. Thisrestricts detailed band analysis and quantitative calculations.

PROCEDURE

Position the diffuse reflectance accessory in the sample compartment of thespectrophotometer and plug it in. Align the optical system according to the manufactures

operating instructions and let the instrument warm up for a few minutes.

Set up the measuring program: wavelength range(s) of interest, mode (reflectance orabsorbance), double beam, and scan speed.

When the instrument is ready, place one of the reference disks over the sample port andthe other over the reference port.

Alternatively, prepare two standards from barium sulfate powder. To do this, place theholder over a frosted plate glass or a flat surface covered with unglazed paper. Add therequired amount of barium sulfate powder in several layers and distribute it uniformly in


31/39


the hole. Press it firmly with the plunger to obtain the required packing density and a

thickness >3 mm. Remove the plunger and check that the barium sulfate surface is perfectly flatthis is

required to minimize phase angle effects.

Remove loose particles remaining on the surface with the aid of a gentle jet of filtered dryair before placing the holder over the instrument port.

Collect the baseline scan with the standard in place and replace the standard on thesample port with the soil sample. Take a subsample of 200 to 500 mg and grind it for 8 to

10 min, or until any apparent grittiness disappears and further grinding causes no

apparent color change. Press the resulting powder into the holder hole, as for the bariumsulfate powder, to a minimum thickness of 3 mm.

Place the holder on the sample port, and record the spectrum. Unless time for spectrumacquisition is limited, it is recommended for most purposes to obtain reflectance

measurements in 0.5- to 1-nm steps for instruments with a wavelength bandwidth of 2

nm. This can take 10 to 20 min for the visible (380750 nm) range, or 20 to 30 min forthe visible-near IR range, in most spectrophotometers.

APPLICATIONS

I denti fi cation of M ineral Species

Some common soil minerals can be identified by their characteristic bands in the absorbance or

KM function spectra. By far, iron oxides have been the most intensively examined soil minerals

to date.

Elucidation of Crystal Properti es The decisive influence of crystal parameters on the position and intensity of the

absorption bands of many minerals is well documented. The spectral features of the different minerals have usually been interpreted in light of the

crystal field and ligand field theories. Used to elucidate the structural properties of Fe oxides. Diffuse reflectance spectroscopy has also been used to characterize nonmetric surface

precipitates.

Quant itati ve Analysis

Applications of IR spectroscopy to qualitative analysis are mainly for the identification ofunknown compounds.

Quantitative analyses are also performed by measuring the intensity of the characteristicbands for each mineral in the KM spectral curve.


32/39


Based on it, at any wavelength, the KM function for a mixture of a small amount of acolored mineral in a matrix of white or colorless soil minerals is proportional to, and

depends almost exclusively on, the concentration of that mineral provided S is constant.

Quali tative Analysis:

It can rapidly estimate the concentration of an element with an accuracy of perhaps oneorder of magnitude. The sensitivity of spectrographic methods depends upon the natureand amount of sample, the type of excitation, and the instrument employed.

Other applications include determination of

Assay of the compound Surfactant chain length determination Hydrogen analysis Iodine value Moisture analysis


33/39


X-RAY DIFFRACTION ANALYSIS

INTRODUCTION

X-ray powder diffraction (XRD) is one of the most powerful technique for qualitative and

quantitative analysis of crystalline compounds. The technique provides information that cannot

be obtained any other way. The information obtained includes types and nature of crystalline

phases present, structural make-up of phases, degree of crystallinity, amount of amorphouscontent, microstrain & size and orientation of crystallites.

Fundamental Principles

Max von Laue, in 1912, discovered that crystalline substances act as three-dimensional

diffraction gratings for X-ray wavelengths similar to the spacing of planes in a crystal lattice. 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. Theinteraction of the incident rays with the sample produces constructive interference (and a

diffracted ray) when conditions satisfyBragg's Law(n=2dsin ). This law relates the

wavelength of electromagnetic radiation to the diffraction angle and the lattice spacing in acrystalline sample. These diffracted X-rays are then detected, processed and counted. By

scanning the sample through a range of 2angles, 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 aset of unique d-spacings. Typically, this is achieved by comparison of d-spacings with standard

reference patterns.

All diffraction methods are based ongeneration of X-raysin 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 crystaldiffraction vary in instrumentation beyond this.

BRAGGS LAW AND ITS EQUATION:

DIFFRACTION OF X-RAYS THROUGH CRYSTAL:

The nature of x-rays is electromagnetic i.e. they are electromagnetic waves. X-rays havevery short wavelength of the order of 10 x 10 -10 m. Therefore it is not possible to produce

interference fringes of x-rays by Young's double slit experiment or by thin film method. The
http://serc.carleton.edu/research_education/geochemsheets/BraggsLaw.htmlhttp://serc.carleton.edu/research_education/geochemsheets/BraggsLaw.htmlhttp://serc.carleton.edu/research_education/geochemsheets/BraggsLaw.htmlhttp://serc.carleton.edu/research_education/geochemsheets/xrays.htmlhttp://serc.carleton.edu/research_education/geochemsheets/xrays.htmlhttp://serc.carleton.edu/research_education/geochemsheets/xrays.htmlhttp://serc.carleton.edu/research_education/geochemsheets/xrays.htmlhttp://serc.carleton.edu/research_education/geochemsheets/BraggsLaw.html


34/39


reason is that the fringe spacing is D x = lL/dand unless the slits are separated by a distance of

10 x 10 -10 m, the fringes so obtained will be closed together that they cannot be observed.

However it is possible to obtain x-rays diffraction by making use of crystals such as rock salt in

which the atoms are uniformly spaced in planes and separated by a distance of order of 2 A to

5A. Therefore, the diffraction of x-rays takes place when they incident on the surface of crystals.

BRAGGS EQUATION:

Consider a set of parallel lattice planes having spacing 'd'between each other as shown.

Consider two rays 'a' and 'b' incident on the surface of crystal of NaCl. After reflection, these

rays reflected and are in phase. After reflection they interfere each other.

The path difference between the two reflected rays is given by:


35/39


Now the X-rays will interfere constructively if the path difference is an integral multiple

of wavelengths.

This relation is known as Bragg's Law. The spacing of the atomic layers of crystals canbe found from the density and atomic weight. Both 'm'and 'q'can be measured and hence the

wave length of x-rays can be measured by using Bragg's equation.

QUANTITATIVE ANALYSIS

XRD can be used not only for qualitative identification but also for quantitativeestimation of various crystalline phases.

This is one of the important advantage of X-ray diffraction technique. Several methods have been proposed and successfully used to quantify crystalline phases

in mixtures. They include external standard methods, the reference-intensity-ratio (RIR)method, chemical methods and the whole pattern fitting Rietveld method.

Of the available methods, the Rietveld method is probably the most accurate and reliablemethod.

The Rietveld method is a whole-pattern fitting least squares refinement technique andhas been successfully used for quantification and characterization of inorganic andorganic compounds It has also been used for crystal structure refinement, to determine

size and strain of crystallites.

INSTRUMENTATION

It consists of The X-ray tube. The flat specimen (labeled sample in the diagram) The microdiffractometer includes a goniometer with a triple-axis sample oscillation

mechanism (T, P, N), an X, Y, Z stage, and a goniometer head.

The goniometer circle (labeled measuring circle in the diagram) which remains constantthrough the analysis and is defined by the position of the target in the X-ray tube, the

center of the sample, and the position of the receiving slit (labeled detector diaphragm)

on the detector side.


36/39


The X-ray tube, specimen and receiving slit also lie on the arc of the focusing circle. Unlike the goniometer circle which remains fixed, the radius of the focusing circle is a

function of -2, with theradius decreasing as increases.

The incident angle defined as the angle between the incident beam and the sample, and2 defined as the angle between the incident and diffracted beams. The detector is moved

at twice the angular rate of the sample to maintain the -2 geometry.

A filter (on the diffracted beam side) is to remove all but the desired K radiationfromthe diffracted beam before it enters the detector.

A slit on the incident beam side is used to narrow the beam so that it is confined withinthe area of the specimen.

The path AB=BC is the radius of the diffractometer circle. The tube position is fixed and the -2 geometry is maintained by rotating the sample

holder at the angular rate of the detector.

There are Soller slits on both the tube and detector side, and two collimating andreceiving slits.

Note the easy-to-read angular indicators and micrometer dials for visually reading and2.

The detector on this system also includes a graphite monochromator adjacent to thescintillation detector eliminating the need for any filters in the system

SamplePreparation

The Ideal Specimen is a statistically infinite amount of randomly oriented powder with crystallite

size less than 10 m, mounted in a manner in which there is no preferred crystallite orientation.


37/39


In this day of automated data collection and analysis, the preparation of your specimen is usually

the most critical factor influencing the quality of your analytical data.

GenerateAnalyticalX-Rays

A coherent beam of monochromatic X-rays of known wavelength is required for XRDAnalysis Striking a pure anode of a particular metal with high-energy electrons in a

sealed vacuum tube generates X-rays that may be used for X-ray diffraction. Copper (Cu) X-ray tubes are most commonly used for X-ray diffraction of inorganic

materials.

The wavelength of the strongest Cu radiation (K) is approximately 1.54 angstroms ().Other anodes commonly used in X-ray generating tubes include Cr (K 2.29 ), Fe (K

1.94 ), Co (K 1.79 ), and Mo (K 0.71 ).

The radiation produced in the tube includes K1, K2, and K as the highest energy X-rays and a whole host of lower energy radiation. We generally use the K for our analytical work. The K radiation is usually removed by use of a filter, a monochromator or an energy-

selective detector.

The K2 radiation is removed from the X-ray data electronically during data processing.Direct t he X-rays at a powdered specimen

In most powder diffractometers systems a series of parallel plates arranged parallel to theplane of the diffractometer circle and several scatter and receiving slits are used to create

an incident beam of X-rays that are parallel. Soller slits are commonly used on both the incident and diffracted beam, but this will

vary depending on the particular system.

The scatter may be varied to control the width of the incident beam that impinges uponthe specimen and the receiving slits may be varied to control the width of the beamentering the detector.

Filters for removing K may be located in the beam path on the generator or detector sideof the path; a monochromator, if present, is usually located on the detector side between

the receiving slit and the detector.

APPLICATIONS

Metals have found applications in thin-film technology due to their luster and highelectrical conductivity.


38/39


Decorative and anticorrosion coatings of chromium, zinc and derivative alloys forarmatures, metal work, kitchen fittings, automotive parts, etc., are mostly deposited by

electroplating.

The technique of gilding of jewelry, porcelain, relics, etc., by gold leaf of onlymicrometers in thickness has been continuously developed for more than 4000 years.

X-ray powder diffraction is most widely used for the identification of unknowncrystalline 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 With specialized techniques, XRD can be used to: Determine crystal structures using Rietveld refinement. Determine of modal amounts of minerals (quantitative analysis)Characterize thin films samples by:

Determining lattice mismatch between film and substrate and to inferring stress andstrain.

Determining dislocation density and quality of the film by rocking curvemeasurements.

Measuring super lattices in multilayered epitaxial structures. Determining the thickness, roughness and density of the film using glancing

incidence X-ray reflectivity measurements.

Make textural measurements, such as the orientation of grains, in a polycrystallinesample.


39/39

References

www.pharmainfo.net. www.wikipedia.com www.pharma-books.blogspot.com www.pharmamirror.com Skoog, Douglas A., F. James Holler and Timothy Nieman (1998). Principles of Instrumental

Analysis (5 ed.). New York. pp. 805808. ISBN 0-03-002078-6.

Methods of pharmaceutical analysis: Roger E Schirmer. Instrumental methods of chemical analysis H.Kaur.

Text book of qualitative chemical analysis Vogels.

Encyclopedia of pharmaceutical technology third edition edited by James Swarbrick.
http://www.pharmainfo.net/http://www.pharmainfo.net/http://www.wikipedia.com/http://www.wikipedia.com/http://www.pharma-books.blogspot.com/http://www.pharma-books.blogspot.com/http://www.pharma-books.blogspot.com/http://www.pharma-books.blogspot.com/http://www.pharma-books.blogspot.com/http://www.pharmamirror.com/http://www.pharmamirror.com/http://www.pharmamirror.com/http://www.pharmamirror.com/http://www.pharmamirror.com/http://www.pharma-books.blogspot.com/http://www.wikipedia.com/http://www.pharmainfo.net/

physical pharmaceutics

Documents