Micromeritics

This is pdf note on the topic Micromeritics specially designed for S Y Bpharm Students (PCI Syllabus)

1. UNIT-IV 10Hrs.
Micromeritics:
Particlesizeanddistribution,meanparticlesize,numberandweightdistribution,
particlenumber,methodsfordeterminingparticlesizebydifferentmethods,
countingandseparationmethod,particleshape,specificsurface,methodsfor
determiningsurfacearea,permeability,adsorption,derivedpropertiesof
powders,porosity,packingarrangement,densities,bulkiness&flowproperties.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

2. MICROMERITICS
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

3. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
https://youtu.be/ExvzdUA6Ed0
Micromeritics introduction

4. Definition: It is the science and technology of small particles.
* Given by DallaValle
Theunitofparticlesizeused,micrometer(µm),micron(µ).
Micron(µm)[1µm=10
–6
m=10
–4
cm=10
–3
mm]
*Asparticlesizedecreases,areaincreases
Micromeritics
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

5. 1.Release and dissolution
Particlesizeandsurfaceareainfluencethereleaseofadrugfroma
dosageform.
Highersurfaceareaallowsintimatecontactofthedrugwiththe
dissolutionfluidsin-vivoandincreasesthedrugsolubilityand
dissolution.
2.Absorption and drug action
Particlesizeandsurfaceareainfluencethedrugabsorptionand
subsequentlythetherapeuticaction.
Higherthedissolution,fastertheabsorptionandhencequickerand
greaterthedrugaction.
Importance of micromeritics in pharmacy
Size and size range of particles are very important in pharmacy.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

6. 3.Physical stability
Theparticlesizeinaformulationinfluencesthephysical
stabilityofthesuspensionsandemulsions.
Smallerthesizeoftheparticle,betterthephysicalstabilityof
thedosageform.
4.Dose uniformity
Goodflowpropertiesofgranulesandpowdersareimportantin
themanufacturingoftabletsandcapsules.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

7. 5.Determination of pore size of filters
Foraccuratedeterminationofporesizeoffiltersthesizeof
particlesarerequired.
4.Coating of Antigens
Antigensarecoatedonadsorbentparticleswheretheparticle
sizeisimportantforuniformdosecalculation.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

8. Apowdersampleischaracterizedbythreethings:
a)Shapeoftheparticles,
b)Sizeoftheparticlesand
c)ParticleSizedistribution
Fundamental properties
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

9. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
https://youtu.be/307cVsjR2_k
Shape of the Particles

10. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
https://youtu.be/_BHE1ma7e78
Particle size and
Equivalent diameter

11. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
https://youtu.be/8lmWaz7CygU
Average Particle Size
and Particle Size
Distribution

12. Particle Size
Thesizeofasphereisreadilyexpressedintermsofitsdiameter.
Diameterofsphere =2r
Thesurfaceareaofsphereis=4πr
2
Volumeofsphere =4/3πr
3
Generallypharmaceuticalpowdersarenon-sphericalinnatureand
theirsurfaceareaandvolumechangewithdimension.Thereforeitis
difficulttoexpressthesizeasameaningfuldiameter.
Insuchcaseitisexpressedintermsofequivalentsphericaldiameters.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

13. TheSurfacediameter,d
s,isthediameterofaspherewiththesame
surfaceareaastheparticle.
TheVolumediameter,d
v,isthediameterofaspherewiththesame
volumeastheparticle.
TheProjecteddiameter,d
p,isthediameterofaspherewiththesame
projectedareaobservedundermicroscope.
TheStokesdiameter,d
st,isthediameterwhichdescribesanequivalent
sphereundergoingsedimentationatthesamerateastheparticle.
TheSievediameter,d
sieve,isthediameterofaspherethatwilljustpass
throughthesameaperturesizeastheparticle.
Thevolumesurfacediameter,d
vs,isthediameterofaspherethathas
thesameratioofsurfaceareatovolumeasfortheparticle.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

14. AverageParticleSize
Wecanconductamicroscopicexaminationofasampleofapowder
andrecordthenumberofparticles.
Particleslyingwithinvarioussizerangescanbeobtainedanddata
canbeplottedshowninTable.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

15. Edmundsonderivedageneralequationfortheaverageparticlesize,
whetheritbeanarithmetic,geometricoraharmonicmeandiameter
�
����=
??????��
�+�
??????��
�
�/�
n=thenumberofparticles.
d=equivalentdiameters.
p=anindexrelatedtothesizeofanindividualparticle(becaused
raisedtothepowerp=1,p=2,orp=3isanexpressionoftheparticle
length,surface,orvolume,respectively.)
Thevalueoftheindexpalsodecideswhetherthemeanis;
arithmetic(ifpispositive),
geometric(ifpiszero),or
harmonic(pisnegative).
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

16. Foracollectionofparticles,thefrequencywithwhichaparticleina
certainsizerangeoccursisexpressedbynd
f
.
Whenthefrequencyindex,f,
hasvaluesof0,1,2,or3,then
thesizefrequencydistribution
isexpressedintermsofthe
totalnumber,length,surface,
orvolumeoftheparticles,
respectively.
Statistical diameters
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

17. Ifalltheparticleshavesamediameterthenthepowdersampleis
calledamonodispersesystem,butifalltheparticlesarenotof
equalsizesthenthatpowdersampleiscalledpolydispersesystem.
Mostofthepharmaceuticalpowdersanddispersionare
polydispersesystems.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

18. Anycollectionofparticlesisusuallypolydisperse.Itis
thereforenecessarytoknownotonlythesizeofacertain
particle,butalsohowmanyparticlesofthesamesizeexistinthe
sample.
Thus,weneedanestimateofthesizerangepresentandthe
numberofeachparticlesize.
Thisistheparticle-sizedistributionandfromitwecancalculate
anaverageparticlesizeforthesample.
Particle Size Distribution
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

19. Whenthenumberofparticleslyingwithinacertainsizerangeis
plottedagainstthesizerangeormeanparticlesize,agraphis
obtained,thatiscalledasfrequencydistributioncurve.
Thewidthofhistogramrepresentthesizerange,andtheheight
representthefrequencyofoccurrenceineachsizerange.
Thisisimportantbecauseitispossibletohavetwosampleswith
thesameaveragediameterbutdifferentdistributions.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

20. NumberandWeightDistributions
ThedatainTableareshownasanumberdistribution,astheywere
collectedbyacountingtechniquesuchasmicroscopy.
Wecangetdatabasedonaweight,ratherthananumber,
distribution.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

21. Itispossibletoconvertthenumberdistributiontoaweightdistributionand
viceversa.
Asthegeneralshapeanddensityoftheparticlesareindependentofthesize
rangepresentinthesample,anestimateoftheweightdistributionofthedata
inTablecanbeobtainedbycalculatingthevaluesshownincolumns9and
10.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

22. Thesignificantdifferencesinthetwodistributionsisapparent,even
thoughtheyrelatetothesamesample.
Forthisreason,itisimportanttodistinguishcarefullybetweensize
distributionsonaweightandanumberbasis.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

23. ParticleNumber
Asignificantexpressioninparticletechnologyisthenumberof
particlesperunitweight,N,whichisexpressedintermsofd
vn·
Thenumberofparticlesperunitweightisobtainedasfollows.
Assumethattheparticlesarespheres,
Thevolumeofsingleparticleis=
��
�
�
Themassis=
��
�
�
�
Thenumberofparticlespergramisthenobtainedfromtheequation
�=
�
��
�
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

24. Methods for determining particle size
Manymethodsavailablefordeterminingparticlesizesuchas;
1.Separationmethods
A.Sieving.
B.Sedimentation.
2.Countingmethods
A.Opticalmicroscopy.
B.Conductivitymethod.
3.Surfaceareadetermination
A.Airpermeability
B.Adsorption
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

25. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
https://youtu.be/MtbfJy3LIsQ
Methods for
determination of Particle
size & Particle size
distribution.

26. A guide to range of particle sizes applicable to each method is;
Particle sizeMethod
<1m Electronmicroscope,
Ultracentrifuge,
Adsorption
1–100m Opticalmicroscope,
Sedimentation,
Coultercounter,
Airpermeability
50m Sieving
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

27. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
https://youtu.be/E4WoS5Vth6o
Sieve Analysis

28. Sieving
(range: 50-1200 µm)
Standardsizesievesareavailabletocovera
widerangeofsize.
Powderisplacedonthepreviouslyarranged
setofsievesinwhichthesievesare
arrangedindecreasingorderoftheirmesh
size.
Thesetofsieveisshakenforafixedperiod
(1to5min),usingmechanicalshaker.
Thematerialwhichisretainedoneachsieve
iscollected&weighseparatelytoobtain
frequencydistributioncurve.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

29. Advantages
Easy to perform, simple
Wide size range
Inexpensive
Disadvantages
Known problems of reproducibility.
Wear/damage of sieve in use or cleaning.
Irregular/agglomerated particles cause misinterpretation.
Rod-like particles : overestimate of under-size.
Duration of shaking may alter the result.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

30. Sedimentation
(range: 0.08-300 µm)
Methodsdependonthefactthattheterminalvelocityofa
particleinafluidincreaseswithsize.
Stokes’equationorStokes’slaw
&#3627408535;=
&#3627408521;
&#3627408533;
=
&#3627408517;
&#3627408532;&#3627408533;
&#3627409360;
&#3627409222;
&#3627409359;−&#3627409222;
&#3627409360;&#3627408416;
&#3627409359;??????&#3627409212;
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

31. &#3627408517;
&#3627408532;&#3627408533;=
&#3627409359;??????&#3627409212;
&#3627409222;
&#3627409359;−&#3627409222;
&#3627409360;&#3627408416;
&#3627408521;
&#3627408533;
&#3627408517;
&#3627408532;&#3627408533;= Stokes’s diameter
&#3627408521;= distance of fall in time t
&#3627409222;
&#3627409359;= density of particles
&#3627409222;
&#3627409360;= density of dispersion medium
&#3627409212;= viscosity of medium
&#3627408416;= gravitational acceleration.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

32. AndreasenPipette
A1%or2%suspensionoftheparticlesinamedium
containingasuitabledeflocculatingagentis
introducedintothevesselandbroughttothe550-ml
mark.
Thestopperedvesselisshakentodistributethe
particlesuniformlythroughoutthesuspension,and
theapparatus,withpipetteinplace,isclamped
securelyinaconstant-temperaturebath.
Atvarioustimeintervals,10mlsamplesare
withdrawnanddischargedbymeansofthetwo-way
stopcock.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

33. Thesamplesareevaporatedandweighedoranalyzedbyother
appropriatemeans.
Theparticlediametercorrespondingtothevarioustimeperiodsis
calculatedfromStokes'slaw.
hinequationbeingtheheightoftheliquidabovethelowerendofthe
pipetteatthetimeeachsampleisremoved.
Theresidueordriedsampleobtainedataparticulartimeistheweight
fraction.
Thecumulativepercentagebyweightundersizecanthenbeplotted
onaprobabilityscaleagainsttheparticlediameter
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

34. Disadvantages
Sedimentationanalysesmustbecarriedoutatconcentrations
whicharesufficientlylowforinteractiveeffectsbetweenparticles
tobenegligible.
Largeparticlescreateturbulence.
Carefultemperaturecontrolisnecessary.
Particlere-aggregationduringextendedmeasurements.
Particleshavetobecompletelyinsolubleinthesuspendingliquid.
Advantages
Equipmentrequiredcanberelativelysimpleandinexpensive.
Canmeasureawiderangeofsizeswithconsiderableaccuracy
andreproducibility.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

35. Conductivitymethod/Coultercounter
Particlesizerangingfrom0.5to500μmismeasuredbythis
method.
Inthismethodparticlevolumeismeasuredandconvertedinto
particlediameter.
Sizeisexpressedasvolumediameter,d
v.
Thisisquick&accuratemethod.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

36. Particlesaresuspendedinaconductingelectrolyteandplacedinbeaker.
TheelectrolytesolutionisfilledInsamplecell,thathasanorificeand
maintaincontactwiththeexternalmedium.
Electrodes are placed in
the solution (in side the
cell) and suspension
outside.
A known volume of a
dilute suspension is
pumped through the
orifice.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

37. Aconstantvoltageisappliedacrosstheelectrodestoproducea
current.
Astheparticletravelsthroughtheorifice,itdisplacesitsownvolume
ofelectrolyte,andthisresultsinanincreasedresistancebetweenthe
twoelectrodes.
Thechangeinresistance,whichisrelatedtotheparticlevolume,
causesavoltagepulsethatisamplifiedandfedtoapulse-height
analyzercalibratedintermsofparticlesize.
Theinstrumentrecordselectronicallyallthoseparticlesproducing
pulsesthatarewithintwothresholdvaluesoftheanalyzer.
Bysystematicallyvaryingthethresholdsettingsandcountingthe
numberofparticlesinaconstantsamplesize,itispossibletoobtaina
particle-sizedistribution.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

38. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

39. Advantages
4000particlespersecondcanbecounted.Thereforesize
distributionanalysiscanbecompletedinrelativelyshorttime.
It gives accurate results.
Disadvantages
Unsuitable for polar and highly water soluble materials due to
solvation.
Instrument is expensive.
Applications
In study of;
Particle growth in suspension and solution.
Dissolution of drugs in desired medium
Effect of antibacterial agent on the growth of micro-organism.
Size distributions of the mineral part of human kidney stones.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

40. By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa
https://youtu.be/bzcc_DqHvqM
Optical Microscopy

41. Themicroscopeeyepieceisfittedwithamicrometerbywhich
thesizeoftheparticlesmaybeestimated.
Optical microscopy
(range: 0.2-100 µm)
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

42. Accordingtotheopticalmicroscopicmethod,powderisdirectly
sprinkledonglassslide(oranemulsionorsuspensiondropis
mountedonruledslideonamechanicalstage.)
Themicroscopeeyepieceisfittedwithamicrometer(ocular
micrometeroreyepiecescale)whichiscalibratedbyusingstage
micrometer.
Bymatchingtheparticleagainsttheeyepiecescale,thesizeofthe
particlescanbeestimated.
Theordinarymicroscopeusedformeasurementtheparticle-sizeinthe
rangeof0.2toabout100µm.
Forreproducibleresultatleast300-500particlesmustbeobserved.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

43. Theparticlesaremeasuredalonganarbitrarilychosenfixedline,
generallymadehorizontallyacrossthecenteroftheparticle.
Popularmeasurementsarethe
1.Feretdiameter
2.Martindiameter
3.projectedareadiameter.
Martin's diameter is the length of a
line that bisects the particle image.
Feret'sdiameteristhedistancebetweentwotangentsonoppositesidesof
theparticleparalleltosomefixeddirection,theydirection.
Projectedareadiameteristhediameterofacirclewiththesameareaas
thatoftheparticleobservedperpendiculartothesurfaceonwhichthe
particlerests.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

44. Disadvantages
1.Thediameterisobtainedfromonlytwodimensionsoftheparticle.
2.Thenumberofparticlesthatmustbecounted(300-500)toobtaina
goodestimationofthedistributionmakesthemethodsomewhatslow
andtedious.
3.Notsuitableforextremelysmallparticles.
4.Unknowinglysameparticlemaybeobservedrepeatedly.
Advantages
1.Simplemethod.
2.Particlesareeasilyobserved.
3.Agglomerationandcontaminationofparticlescanbedetected.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

45. Thegeometricshapeandsurfaceconditionofparticlesreferstoshape
ofparticles.
Particlesmaybespherical,rounded,elongated,acicular,angularetc.
Iftheshapeofaparticleisperfectlysphericalitiseasytoexpressit
byitsdiameter;butifitisnotsphericalthenitbecomesverydifficult
toexpress.Hence,equivalentdiametersaretakenintoconsideration.
Mostofthepharmaceuticalparticlesarenotperfectlyspherical.
Particleshapeaffectsthephysicochemical,biopharmaceutical
propertiesofformulation.
Particle Shape
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

46. Particle shape and surface area
Theshapeaffectstheflowandpackingpropertiesofapowder,as
wellashavingsomeinfluenceonthesurfacearea.
Thesurfaceareaperunitweightorvolumeisanimportant
characteristicofapowderinadsorptionanddissolutionrate
studies.
Aspherehasminimumsurfaceareaperunitvolume.
Themoreasymmetricaparticle,thegreateristhesurfaceareaper
unitvolume.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

47. Thesurfaceareaorvolumeofaspherecanbecalculatedsimplyby
??????&#3627408430;??????&#3627408415;????????????&#3627408414;????????????&#3627408414;??????=&#3627409221;&#3627408517;
&#3627409360;
????????????&#3627408421;&#3627408430;&#3627408422;&#3627408414;=
&#3627409221;&#3627408517;
&#3627409361;
&#3627409364;
Thesurfaceareaandvolumeofasphericalparticlearetherefore
proportionaltothesquareandcube,respectively,ofthediameter.
Toobtainthesurfaceorvolumeofaparticleswhoseshapeisnot
sphericalonemustchooseanequivalentdiameterthroughcorrection
factor(e.g.formicroscopicmethod,projecteddiameter,d
p)
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

48. Bymeansofproportionalityconstants,wecanthenwrite
??????&#3627408430;??????&#3627408415;????????????&#3627408414;????????????&#3627408414;??????=??????
&#3627408532;&#3627408517;
&#3627408529;
&#3627409360;
=&#3627409221;&#3627408517;
&#3627408532;
&#3627409360;
where??????
&#3627408532;isthesurfaceareafactorandd
sistheequivalentsurface
diameter.
Forvolumewewrite
????????????&#3627408421;&#3627408430;&#3627408422;&#3627408414;=??????
&#3627408535;&#3627408517;
&#3627408529;
&#3627409361;
=
&#3627409221;&#3627408517;
&#3627408535;
&#3627409361;
&#3627409364;
Where??????
&#3627408535;,isthevolumefactorandd
v,istheequivalentvolume
diameter.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

49. Thesurfaceareaandvolumefactor“shapefactors”are,inreality,
theratioofonediametertoanother.
Thus,forasphere,
??????
&#3627408532;=
&#3627409221;&#3627408517;
&#3627408532;
&#3627409360;
&#3627408517;
&#3627408529;
&#3627409360;
=&#3627409361;.&#3627409359;&#3627409362;
and
??????
&#3627408535;=
&#3627409221;&#3627408517;
&#3627408535;
&#3627409361;
&#3627409364;&#3627408517;
&#3627408529;
&#3627409361;
=&#3627409358;.&#3627409363;&#3627409360;&#3627409362;
Thereareasmanyofthesevolumeandshapefactorsasthereare
pairsofequivalentdiameters.
Theratio??????
&#3627408532;/??????
&#3627408535;,isalsousedtocharacterizeparticleshape.
Whentheparticleisspherical,??????
&#3627408532;/??????
&#3627408535;=6.0
Themoreasymmetrictheparticle,themorethisratioexceedsthe
minimumvalueof6.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

50. Specificsurface
Specificsurfaceareaisdefinedasthesurfaceperunitweight(S
w)orunit
volume(S
v)ofthematerial.
Itcanbederivedfromequationsgivenabove.
Takingthegeneralcase,forasymmetricparticleswherethe
characteristicdimensionisnotyetdefined,
Sv=
Surfaceareaofparticles
volumeofparticles
Sv=
??????
&#3627408532;&#3627408517;
&#3627409360;
??????
&#3627408535;&#3627408517;
&#3627409361;
=
??????
&#3627408532;
??????
&#3627408535;&#3627408517;
=
&#3627409364;
&#3627408517;
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

51. &#3627408506;
&#3627408536;=
&#3627409364;
&#3627408517;
&#3627408535;&#3627408532;&#3627409222;
&#3627408506;
&#3627408536;=
&#3627408532;
&#3627408535;
&#3627409222;
Thesurfaceareaperunitweighttherefore,
Or
Sw=
??????
&#3627408532;
??????
&#3627408535;&#3627408517;
&#3627408535;&#3627408532;&#3627409222;
Wherethedimensionisnowdefinedas&#3627408517;
&#3627408535;&#3627408532;thevolume-surface
diameter.
Forsphericalparticles
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

52. Theabovemethodofestimationisbasedonparticlediameter
data.Itcanbeusedtoestimatethespecificsurfaceareafornon
poroussolids.
Forporousmaterialsfollowingmethodsareused;
1.Adsorptionmethod
2.Airpermeabilitymethod
Powder surface area-Methods
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

53. Adsorption method
Particleshavinglargespecificsurfaceareaaregoodadsorbent
ofgasesandsoluteformsolution.
Amountofgasorsolutethatisadsorbedtoform
monomolecularlayerontheadsorbentisafunctionofsurface
areaofthepowder.
Principle
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

54. Inthismethodsolutefromsolutionisadsorbedonthesurfaceoftest
materialwhosesurfaceareaistobedetermined.
Aknownquantityofmaterial(adsorbent)isaddedtosolutionandstirred
forsufficientperiodtoattainadsorptionequilibrium.
Themixtureisthefilteredandfiltrateisanalyzedtofindunadsorbed
amountofsolute.Thedifferenceinamountaddedandthatofamount
unadsorbedgivesamountofsoluteadsorbed.
Fromtheknowledgeofcross-sectionalareaofamoleculeandtotalnumber
ofsolutemoleculesadsorbed,itispossibletocalculatethesurfaceareaof
testmaterial.
Apracticalexampleofthistypeisdeterminationofsurfaceareaof
activatedcharcoalbyadsorptionmethodusingaqueousaceticacidsolution.
Monolayer solution adsorption
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

55. Determinationofsurfaceareaiscarriedoutbygasadsorptionmethodusing
aninstrumentcalledQuantsorb.
Apowdermaterialwhosesurfaceareaistobedeterminedisplacedintoa
celloftheinstrument.Thenitrogengasisusedasadsorbate.
Helium,aninertgas,whichisnotadsorbed,isalsopassedthroughthe
powderinacell.
Athermalconductivitydetectormeasurestheamountofnitrogenadsorbed
ateveryequilibriumpressure.
Abell-shapedcurveisobtainedonastrip-chartrecordingsystem.
Theheightofsignalgivestherateofadsorptionofnitrogenandthearea
underthecurveiscalculatedtoobtaintheamountofgasadsorbedon
powdersample.
Adsorption of gas on powders
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

56. Air permeability method
Powderispackedinthesampleholderasacompactplug.Inthis
packing,surface-surfacecontactbetweenparticlesappearasaseriesof
capillaries.Thesurfaceofthiscapillariesisafunctionofthesurface
areaofpowder.
Whenairisallowedtopassthroughthepowderbedataconstant
pressure,thebedresisttheflowofair.Thisresultsinthepressuredrop.
Thegreaterthesurfaceareapergramofpowder,S
w,thegreaterthe
resistancetoflow.
Thepermeabilityofairforagivenpressuredropisinversely
proportionaltospecificsurface.
Principle
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

57. Itconsistofsampletubecontainingthepackedpowdersamplewithoneend
connectedtoanairpumpthroughaconstantpressureregulator.Theotherend
isattachedtoacalibratedmanometer.
Fisher subsieve sizer
Pressure
Varies
with
particle
size
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

58. Working
Theairpumpbuildupairpressureandisconnectedtoa
constantpressureregulator.
Airispassedthroughtheairdryertoremovemoisture.
Airisthenallowedtoflowthroughthepackedpowderinthe
sampletube.
Theflowofairismeasuredbymanometer.
Thelevelofthefluidinmanometerindicatetheaverage
diameteroftheparticles.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

59. The Koezeny-carmanequation is used to estimate the surface area by
this method
&#3627408509;=
&#3627408488;
&#3627409212;&#3627408532;
&#3627408536;
&#3627409360;
∆??????&#3627408533;
??????&#3627408525;
??????
(&#3627409359;−??????)
&#3627409360;
Where,
A= cross sectional area of bed (pack), cm
2
∆??????= pressure difference of plug
t= time of flow, seconds
l= length of the sample holder
??????= porosity of powder
S
w= surface area per gram of powder, cm
2
/g
&#3627409212;= viscosity of air
K= a constant of irregular capillaries
V= volume of air flowing through the bed, cm
3
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

60. Derived properties of powders
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

61. 1.Truedensity:Thetruedensityofasampleexcludesthevolume
oftheporesandvoidswithinthepowdersample.
&#3627408507;&#3627408531;&#3627408534;&#3627408518;&#3627408517;&#3627408518;&#3627408527;&#3627408532;&#3627408522;&#3627408533;&#3627408538;=
&#3627408510;&#3627408518;&#3627408522;&#3627408520;&#3627408521;&#3627408533;&#3627408528;&#3627408519;&#3627408529;&#3627408528;&#3627408536;&#3627408517;&#3627408518;&#3627408531;
&#3627408533;&#3627408531;&#3627408534;&#3627408518;&#3627408535;&#3627408528;&#3627408525;&#3627408534;&#3627408526;&#3627408518;&#3627408528;&#3627408519;&#3627408529;&#3627408528;&#3627408536;&#3627408517;&#3627408518;&#3627408531;
2.Bulkdensity:Thebulkdensityvalueincludesthevolumeofall
oftheporeswithinthepowdersample.
&#3627408489;&#3627408534;&#3627408525;&#3627408524;&#3627408517;&#3627408518;&#3627408527;&#3627408532;&#3627408522;&#3627408533;&#3627408538;(&#3627409222;)=
&#3627408500;&#3627408514;&#3627408532;&#3627408532;&#3627408528;&#3627408519;&#3627408529;&#3627408528;&#3627408536;&#3627408517;&#3627408518;&#3627408531;(&#3627408536;)
&#3627408489;&#3627408534;&#3627408525;&#3627408524;&#3627408535;&#3627408528;&#3627408525;&#3627408534;&#3627408526;&#3627408518;(&#3627408509;&#3627408515;)
Density of powders
Truevolume(V
P)=volumeofpowderitself.
Bulkvolume(V
b)=truevolume+volumeofspacesbetweenparticles
Densityisdefinedasweightperunitvolume(W/V).
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

62. Bulkdensityisusedtochecktheuniformityofbulkchemical
(Q.C.measures).
Thesizeofcapsuleismainlydeterminedbybulkvolumefora
givendoseofmaterial.Thehigherthebulkvolume,lowerwillbe
bulkdensity&biggerthesizeofcapsule.
Ithelpsinselectingthepropersizeofcontainer,packingmaterial,
mixingapparatusintheproductionoftabletandcapsule.
Applications of Bulk density
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

63. Porosity
Porosityorvoidfractionisameasureofthevoid(i.e."empty")
spacesinamaterial,andisafractionofthevolumeofvoidsover
thetotalvolume,
Valuesbetween0and1,orasapercentagebetween0%and100%.
Supposeapowder,suchaszincoxide,isplacedinagraduated
cylinderandthetotalvolumeisnoted.Thevolumeoccupiedis
knownasthebulkvolume,Vb.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

64. Voidvolume=Bulkvolume–Truevolume
&#3627408509;=&#3627408509;
&#3627408515;−&#3627408509;
&#3627408529;
Ifthepowderisnonporous,thatis,hasnointernalporesor
capillaryspaces,thebulkvolumeofthepowderconsistsofthe
truevolumeofthesolidparticlesplusthevolumeofthespaces
betweentheparticles.
Thevolumeofthespaces,knownasthevoidvolume,V,isgiven
bytheequation
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

65. Theporosity,orvoids,ε,ofpowderisdefinedas;theratioofthe
voidvolumetothebulkvolumeofthepacking.
??????&#3627408528;&#3627408531;&#3627408528;&#3627408532;&#3627408522;&#3627408533;&#3627408538;(??????)=
&#3627408535;&#3627408528;&#3627408522;&#3627408517;&#3627408535;&#3627408528;&#3627408525;&#3627408534;&#3627408526;&#3627408518;
&#3627408515;&#3627408534;&#3627408525;&#3627408524;&#3627408535;&#3627408528;&#3627408525;&#3627408534;&#3627408526;&#3627408518;
??????&#3627408528;&#3627408531;&#3627408528;&#3627408532;&#3627408522;&#3627408533;&#3627408538;(??????)=
&#3627408515;&#3627408534;&#3627408525;&#3627408524;&#3627408535;&#3627408528;&#3627408525;&#3627408534;&#3627408526;&#3627408518;−&#3627408533;&#3627408531;&#3627408534;&#3627408518;&#3627408535;&#3627408528;&#3627408525;&#3627408534;&#3627408526;&#3627408518;
&#3627408515;&#3627408534;&#3627408525;&#3627408524;&#3627408535;&#3627408528;&#3627408525;&#3627408534;&#3627408526;&#3627408518;
??????=
&#3627408509;
&#3627408515;−&#3627408509;
&#3627408529;
&#3627408509;
&#3627408515;
Porosity is frequently expressed in percent
%??????=&#3627409359;−
&#3627408509;
&#3627408529;
&#3627408509;
&#3627408515;
×&#3627409359;&#3627409358;&#3627409358;
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

66. Porositymeasurement
Porosityofpowderscanbemeasuredby;
1.Directmethod/Tapingmethod
2.Watersaturationmethod
3.Waterevaporationmethod
4.Computedtomographymethod/industrialCTscanning
5.Mercuryintrusionporosimetry
6.Gasexpansionmethod
ApplicationsofPorosity
Porosityinfluencestherateofdisintegrationanddissolution.The
highertheporosity,thefastertherateofdissolution.
Porosityisappliedinthestudiesofadsorption&diffusionofdrug
materials.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

67. PackingArrangements
Powderbedsofuniform-sizedspherescanassumeeithertwoideal
packingarrangements:
(a)closestorrhombohedraland
(b)open,loosest,orcubicpacking.
(a) (b)
Thetheoreticporosityofapowderconsistingofuniformspheres
inclosepackingis26%andforloosestpackingis48%.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

68. Theparticlesinrealpowders,itistobeexpectedthattheparticleof
ordinarypowdersmayhaveanyarrangementintermediatebetweenthe
twoidealpackingsofFigure,anmostpowdersinpracticehave
porositiesbetween30%and50%.
Iftheparticlesareofgreatlydifferentsizes,thesmalleronesmaysift
betweenthelargeronestogiveporositiesbelowthetheoretical
minimumof26%.
Ifpowderscontainingflocculatesoraggregates,whichleadtothe
formationofbridgesandarchesinthepacking,theporositymaybe
abovethetheoreticalmaximumof48%.
Inrealpowdersystems,almostanydegreeofporosityispossible.
Crystallinematerialscompressedunderaforceof100,000lb/in.
2
can
haveporositiesoflessthan1%.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

69. Bulkiness
Specificbulkvolume,thereciprocalofbulkdensity,isoftencalled
bulkinessorbulk.
Itisanimportantconsiderationinthepackagingofpowders.
Thebulkdensityofcalciumcarbonatecanvaryfrom0.1to1.3,and
thelightestorbulkiesttypewouldrequireacontainerabout13
timeslargerthanthatneededfortheheaviestvariety.
Bulkinessincreaseswithadecreaseinparticlesize.
Inamixtureofmaterialsofdifferentsizes,however,thesmaller
particlessiftbetweenthelargeronesandtendtoreducethe
bulkiness.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

70. Flow properties
Itdependsonparticlesize,shape,porosity,moisturecontentand
density.
Powdersmaybefree-flowingorcohesive(“sticky”).
Powdertransferthroughlargeequipmentsuchashopper.
Unevenpowderflowmayresultsin…
excessentrappedairwithinpowders→cappingorlamination.
increaseparticle’sfrictionwithdiewallcausinglubrication
problems,andincreasedustcontaminationrisksduringpowder
transfer.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

71. Tests to evaluate the flowability of a powder:
1. Carr’s compressibility index
Avolumeofpowderisfilledintoagraduatedglasscylinderand
repeatedlytappedforaknownduration.Thevolumeofpowder
aftertappingismeasured.
&#3627408490;&#3627408514;&#3627408531;&#3627408531;’&#3627408532;&#3627408522;&#3627408527;&#3627408517;&#3627408518;&#3627408537;%=
&#3627408507;&#3627408514;&#3627408529;&#3627408529;&#3627408518;&#3627408517;&#3627408517;&#3627408518;&#3627408527;&#3627408532;&#3627408522;&#3627408533;&#3627408538;–??????&#3627408528;&#3627408534;&#3627408531;&#3627408518;&#3627408517;&#3627408528;&#3627408531;&#3627408515;&#3627408534;&#3627408525;&#3627408524;&#3627408517;&#3627408518;&#3627408527;&#3627408532;&#3627408522;&#3627408533;&#3627408538;
&#3627408507;&#3627408514;&#3627408529;&#3627408529;&#3627408518;&#3627408517;&#3627408517;&#3627408518;&#3627408527;&#3627408532;&#3627408522;&#3627408533;&#3627408538;
×&#3627409359;&#3627409358;&#3627409358;
Flow description %Compressibility
Excellent flow 5-15
Good 16-18
Fair 19-21
Poor 22-35
Very poor 36-40
Extremely poor >40
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

72. 2. Hausner's ratio
Hausner'sratio=Tappeddensity/Pouredorbulkdensity
Hausner'sratioisrelatedtointerparticlefriction
Valuelessthan1.25indicatesgoodflow.
Valuegreaterthan1.5indicatespoorflow.
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

73. 3. The angle of repose &#3627409213;
Thefrictionalforcesinaloosepowdercanbemeasuredbythe
angleofrepose&#3627409213;.
&#3627408429;??????&#3627408527;&#3627409213;=
&#3627408521;
&#3627408531;
&#3627409213;=themaximumanglepossiblebetweenthesurfaceofapileof
powderandhorizontalplane
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa

74. Thesampleispouredontoahorizontalsurfaceandtheangleofthe
resultingpyramidismeasured.
Theusernormallyselectsthefunnelorificethroughwhichthe
powderflowsslowlyandreasonablyconstantly.
Significance
Angleofreposelessthan20(excellentflow)
Angleofreposebetween20-30(goodflow)
Angleofreposebetween30-34(Passflow)
Angleofreposegreaterthan40(poorflow)
By; Khalifa M. Asif Y. Asst. Professor Ali-Allana College of Pharmacy, Akkalkuwa