Suspensions for B.pharmacy Suspensions in Pharmaceutics

Suspension for B.pharm

2. Suspensionmaybedefinedaspreparation
containingfinelydivideddrugparticles
distributedsomewhatuniformlythroughouta
vehicleinwhichthedrugexhibitsaminimum
degreeofsolubility.
or

3. Suspensionsarethebiphasicliquiddosage
formofmedicamentsinwhichthefinelydivided
solidparticles.
The range of solid particles in suspension from
0.5 to 5.0 micron.
Suspensions are used in orally, parentally and
also externally.
They are chemically stable than solution.

4. •Accordingtotheparticlesizeofthe
dispersedphase,suspensionsaredivided
into:
Coarsesuspension:
whichisadispersionofparticleswithamean
diametergreaterthan1µm.
Colloidalsuspension:
Whichisadispersionofparticleswithamean
diameterlessthan1µm

5. Ifpatienthasadifficultyofswallowingsolid
dosageforms(aneedfororalliquiddosageform).
Fasterrateofdissolutionandoralabsorptionthan
soliddosageforms,yetslowerthansolutions.
Drugsthathaveverylowsolubilityareusefully
formulatedassuspensions.
Drugsthathaveanunpleasanttasteintheir
solubleforms(e.g.,chloramphenicol(soluble)
vs.chloramphenicolpalmitate(insoluble)).

6. Suspensionshouldsettleslowly&shouldbe
readilyredisperseduponshakingofthe
container.
Thesuspensionispourable.
Particlesinsuspensionaresmallandrelatively
uniforminsize.sothattheproductisfreefrom
agrittytexture.

7. Based on General class
→Oral Suspension
e.g. Paracetamol Suspension
→Externally Applied suspension
e.g. Calamine lotion
→Parenteral Suspension
e.g. Insulin zinc suspension

8. Based on proportion of Solid Particles
Dilute Suspension (2 to 10% w/v solid)
e.g. cortisone acetate, predinsolone
acetate
Concentrated Suspension (50% w/v solid)
e.g. Zinc oxide suspension

9. Based on electrokinetic nature of Solid
particle
Flocculated Suspension
Deflocculated Suspension

10. Based on Size of Particle
Coarse Suspension
Suspensions having particle sizes of greater
than about 1micron in diameter are called as
coarse suspensions.
Colloidal Suspension
Suspensions having particle sizes of
suspended solid less than about 1micron in
size are called as colloidal suspensions.

11. Inflocculatedsystemtheindividualparticleare
contactwitheachothertoformlooseaggregate
&createnetworklikestructure.
Rateofsedimentationishigh.
Sedimentislooselypacked.Whenshakingitcan
beredisperseeasily&reformtheoriginal
suspension.
Flocculatedsuspensionsnotbeelegantbecause
theyaredifficulttoremovefrombottlesorvials&
ontransferringfromthebottlethefloccules
remainingstickingtothesideofthebottle.

12. Indeflocculatedsystemtheindividualparticle
areexistasseparateentities.
Rateofsedimentationislow.
Sedimentistightlypacked.Whenshakingitcan
notberedisperseeasily&formthecake.
Deflocculatedsuspensionsbeelegant.They
havepleasingappearancebec.thesubstance
remainsuspendedforsufficientlongtime.

15. Itisdefinedastheformationofa
nonredispersiblesedimentwithinasuspension
system.
CAUSES:Crystalbridging&closedaggregatein
formulation.
Incrystalbridging,particlesurfacecrystal
growthoccursontwoormoreparticles
simultaneouslyinthesteadyformation.

16. Small changes in temperature that occurs during
shelf storage lead to unexpectedly rapid caking
via crystal bridging.
A sedimented, highly coagulate suspension tends
to form large coagules as the surface films
present on coagulated particle causes the filmed
particles to cling to each other.

17. SEDIMENTATION:
Sedimentationmeanssettlingofparticle(or)
flocculesoccurundergravitationalforcein
liquiddosageform.

18. Stokes equation:
d = Diameter of particle
r = radius of particle
V sed.= sedimentation velocity in cm / sec
ρs= density of disperse phase
ρo= density of disperse media
g = acceleration due to gravity
ηo= viscosity of disperse medium in poise

19. Limitation Of Stoke’s Equation.
Stoke'sequationappliesonlyto:
›Sphericalparticlesinaverydilutesuspension
(0.5to2gmper100ml)
›Particleswhichfreelysettlewithoutcollision.
›Particleswithnophysicalorchemicalattraction.

20. Brownianmovementofparticleprevents
sedimentationbykeepingthedispersed
materialinrandommotion.
Brownian movement depends on the density of
dispersed phase and the density and
viscosity of the disperse medium.

21. Brownian movement can be observed,
If particle size is about 2 to 5µm,
When the density of particle & viscosity of
medium are favorable.

22. Zeta Potential
Thezetapotentialdefinedasthedifference
betweenthesurfaceofthetightlyboundlayer
(shearplane)&theelectroneutralregionofthe
solution.
SURFACE
Tightly bound layer
Electroneutral
region

23. Asthepotentialdropsoffrapidlyatfirst,followedmore
gradualdecreaseasthedistancefromthesurface
increases.
Thisisbecausethecounterionsclosetothesurfaceacts
asascreenthatreducetheelectrostaticattraction
betweenthechargedsurfaceandthosecounterions
furtherawayfromthesurface.

24. Zeta potential has practical application in stability
of systems containing dispersed particles .
Since this potential, rather than the Nernst
potential, governs the degree of repulsion
between the adjacent, similarly charged,
dispersed particles.
If the zeta potential is reduced below a certain
value , the attractive forces exceed the repulsive
forces, and the particles come together.

25. Zeta Potential(mV) Stability behaviorof Colloid
From 0 to ±5, Rapid Coagulationor flocculation
From ±10 to ±30 Incipient instability
From ±30 to ±40 Moderate stability
From ±40 to ±60 Good stability
More than ±61 Excellent stability

26. Structuredvehiclealsocalledasthickeningagent
orsuspendingagent.
Theyincreasestheviscosityofthecontinuous
phasesothattheparticlesremainsuspendedfor
asufficientlongtime.
Thesestructuredvehiclesentrappedtheparticle
andreducesthesedimentationofparticles.
Although,thesestructuredvehiclesreducesthe
sedimentationofparticles.

27. Acacia,Tragacanth&sodiumalginatenotvery
commonlyused.
Thesemi-syntheticstructuredvehiclesare
widelyused.
E.g.methylcellulose,CMC,hydroxypropyl
methylcelluloseetc.
Clayssuchashydratedaluminiumsilicateor
magnesiumsilicatealsousedasthickening
agent.

28. Wettingagentorsubstancewhichreducethe
interfacialtensionbetweenthesolidparticle&
liquidphase.
Itisadsorbedatthesolid/liquidinterface,insuch
waythattheaffinityoftheparticlesforthe
surroundingmediumisincreased&interparticular
forcesaredecreased.

29. Theparticles,evenhighdensity,floatonthe
surfaceoftheliquiduntilthelayerofairisdisplaced
completely.
The use of wetting agent allows removing this air
from the surface and to easy penetration of the
vehicle into the pores.
e.g.alcoholintragacanthmucilage,glycerinor
glycolinsodiumalginateetc.
Excessiveamountwettingagentleadtofoamingor
undesirabletasteorodourtosuspension.

30. Flocculatingagentorsurfactantarereducesthe
interfacialtension.
Theyactlike,surfactantwithnegativecharge
areadsorbedontheparticles,minimise
flocculationinthepresenceofpositiveions
becauseofnaturalrepulsionoflikecharge.

31. e.g.ofnegativechargesurfactantsodium
laurylsulphate,sodiumdioctylsulphocinate
etc.
Non-ionicsurfactantalsohavenegative
chargesurfactantinsolution.
Tweens,carbowaxsesarefrequentlyused.

32. Someparticleshavenotsufficientsurface
energy,sothatparticlescometogether&forms
largeparticle.
Toovercomethatdifficultythesubstancemay
beintroducedinthesuspension&thosecalled
dispersingagent.

33. Thesesubstanceincreasethezetapotential&
donotallowtheparticlestocometogetherto
formlargeparticles.
Theyalsoactasstabiliserinsuspension.
e.g.glycerylmonostearate,polyoxethylene
glycol,sorbitanetc.

34. Itshouldeffectiveagainstwiderangeofmicro-
organisms.
Itshouldbephysically&chemicallystable.
Itshouldbenon-toxic&compatiblewithother
addedsubstance.
e.g.benzoicacid,sodiumbenzoate,methyl&
propylparaben.

35. SuspensionContainingDiffusibleSolids
SuspensionContainingIndiffusibleSolids
SuspensionContainingPoorlyWettableSolids
SuspensionProducedbyChemicalReaction

36. Someinsolublesolidsarelight&easily
wettable.
Onthatreason,theyreadilymixwithwater&
onshaking,diffusethroughtheliquidforlong
enoughtoensureevendistributionineach
dose.
Suchsubstanceareknownasdiffusibleor
dispersiblesolids.

37. List of diffusible solids commonly used in oral
preparations
Calcium Carbonate..antacid
Light Kaolin…treat diarrhea
Light Magnesium Carbonate..laxative
Magnesium Trisilicate…antacid
Rhubarb Powder…digestive problems

38. Finely powder
Take insoluble powder in a mortar.
Add sufficient vehicle to produce smooth paste.
Add any non-volatile solid ingredients in part of
the vehicle, and mix well.
Add any volatile solid ingredients, previously
dissolved in some of the vehicle & mix well.
Add any liquid ingredients.

39. Rinsethemortar&pestlewithsuccessive
volumeofvehicleuntiltheyarequietclean,
transferringtherinsingtothebottle.
Makeuptothevolumewithvehicle&shake
thoroughly.
CONTAINER&STORAGE:
Dispensedmedicinesi.e.mixture,lotionetc.
Thickcontainerwithwidemouth.
Storeincoolplace.
Verylowtemp.Maycausesuspended
particlestoaggregated

40. Indiffusibleparticleswillnotdistributedinavehicle
longenough.
Sothatthecorrectingthisproblemistoincreases
theviscosityofthevehiclebyaddingathickening
agent.

41. Used Internally Indiffusible solids
Aspirin..fever & pain
Chalk..antacid
Phenobarbiton..sedative
Sulphadimidine…chalmydia
Used Externally Indiffusible solids
Calamine..pain & itching
Hydrocortisone..inflammation
Sulphur..antibacterial
Zinc oxide..irritation

42. Tragacanthpowdermainlyusedsuspending
agentforthattypeofpreparation.
Tragacanthpowderisusedintheratioof2gm
per100mlofthesuspension.
Tragacanthmucilageitisusedintheratioof¼
th
ofthevolumeofthesuspension.

43. Tragacanthmucilageisusedonlywhenthe
vehicleischloroformwaterorwater.
Bec.Ifitaddedtopreparationscontaininga
medicinallyactivevehicle,themucilagereplace
medicinallyactivevehicle,therebydecreasing
theiractivity.
Insuchcasestragacanthpowdermustbeused
assuspendingagent.

44. FinelypowdertheIndiffusiblesolidparticles
takeinamortar.
Addanydiffusibleorsolublesolids.
Addtragacanthpowderormucilage&mix
thoroughly.
IfonlyIndiffusiblesubstanceistobe
incorporated,mixitwithtragacanthpowderina
mortar.
Addsufficientvehicletoproducesmooth
cream.
Thenaddmorevehicletomakeupthefinal
volume.

45. Somesubstancee.g.sulphur&hydrocortisone
arebothinsolubleinwater&poorlywettedby
it.
Thoseareproduceclumps&itisdifficultto
disperseinaqueousliquids.
Alsoproducefoamonshakingbecauseitis
satbilisedbythefilmofunwettablesolidatthe
liquid/airinterface.

46. Onthatreasonaddedsatisfactorywettingagent,
thosemustbereducedtheinterfacialenergy
betweenthesolid&liquid.
Thoseagentadsorbedatthesolid/liquidinterface
insuchawaythattheaffinityoftheparticlesfor
thesurroundingmediumisincreased,whilethe
interparticularforcesaredecreased.
e.g.alcoholintragacanthmucilage,glycerin&
glycolinsodiumalginate,Quillaiaextractshave
beenusedinsulphurlotionetc.

47. Chemicalreactionmethodareusedtoproduce
insolubleactiveconstituentsinthelotion.
Inthatmethodhighlydilutedsolutionsof
reactingsubstancearemixedtogether.
Soastoformveryfinelydividedprecipitatesthat
canbeeasilydistributedthroughouttheliquidon
shaking.

48. Precipitatessoformedaregenerallydiffusible
innaturethereforenoneedanysuspending
agent.
ZincsulphidelotionB.P.Cproducedbythis
method.

49. Pharmaceuticalsuspensionsfororaluseare
generallypackedinwidemouthcontainer
havingadequatespaceabovetheliquidto
ensurepropermixing.
Parenteral suspensions are packed in either
glass ampoules or vials.

50. It should be inert.
It should effectively preserve the product
from light, air, and other contamination.
It should effectively deliver the product
without any difficulty.
It should be cheap.

51. LABEL:
Shakewellbeforeuse
Donotfreeze
Protectfromdirectlight(forlightsensitive
drugs)
Incaseofdrysuspensionspowderthe
specifiedamountofvehicletobemixedmay
indicatedclearlyonlabel.

52. STORAGE:
Suspensionsshouldbestoredincoolplace
butshouldnotbekeptinarefrigerator.
Freezingatverylowtemperaturesshouldbe
avoidedwhichmayleadtoaggregationof
suspendedparticles.
Storedatcontrolledtemperaturefrom20-25
0
c

53. Dispersionsystemisdefinedasa
heterogenoustwophasesysteminwhich
internal(dispersed,discontinous)phaseis
distributedordispersedwithinthe
continuous(external)phaseorvehicle.
e.g.Suspensions&Emulsions

54. PROPELLER MIXERS
Themostoftenusedmixingimplementis
marinepropellermixer.
Thesemachinesuserounded,pitched,three
bladedesignthatproducesmostlyaxialflow.
Theyprovidegoodflowandblending
capabilitiesinsmallbatchesoflowto
mediumviscosities.

55. Propellersmixerscanbeinstalledonvertical
centerlineorthroughthesidewallofprocess
vessel.
Theycanbeoperatedataround300-400rpm.
Theseareusedmostlyforliquid-liquidblending
applicationsinsome easilyproducible
suspensions.

57. Themostversatileofallmixersinthe
entirespanofmixingequipmentsarethe
axialandradialflowturbines.
Turbinesmixerscanbemadetohandle
hugebatches,evenupto5,00,00gal&
suitableforemulsificationprocess.

58. Radial Flow turbine
Axial flow turbine

59. Itisalsocalledassawbladedisperser.
Thismachineconsistsofavariablespeed
shaftconnectedtoanimpellerwithaserrated
edge.
Thetipspeedissetaround4000ft/min.
Thediameterofimpellershouldbe1/3of
diameterofvessel.

60. Theimpellershouldbelocatedoneimpeller
diameteroffthebottomofvessel
Itcandeagglomeratingparticleswhenthe
viscositiesbetween10,000to20,000cps.
Application:
It is used for pigment dispersion, dye stuffs

61. Limitations:
Air incorporation is another problem so it is
best used for suspensions and not for
emulsions.

62. Itisusedtodispersethesolidsintoliquidsand
toemulsifyliquid-liquidsystems.
Thesegenerallyusedaspolishingmachinesfor
emulsionsorsuspensionsbecausethey
producefineparticleordropletsizeproductto
enhanceaproductsstability.
Theyareoperatedatspeedof3600rpm

64. Types:
1.Triple roll mill
2.Ball mill

65. Athreerollmillortriplerollmillisa
machinethatusesshearforcecreatedby
threehorizontallypositionedrollsrotatingin
oppositedirectionsanddifferentspeeds
relativetoeachother,inordertomix,refine,
disperse,orhomogenizeviscousmaterials
fedintoit.
TRIPLE ROLL
MILL

67. Itisusedforsizereductionfinesoliddiscrete
particlesorfordeagglomerationofverytightly
boundagglomerates.
Themachineconsistsofcylindricaldruminto
whichachargeofheavysphericalballsusually
metalorceramicisloadedalongwiththe
componentsofthedispersion.

69. SEDIMENTATIONMETHOD
Thesuspensionformulation(50mL)waspoured
separatelyinto100mLmeasuringcylindersand
sedimentationvolumewasreadafter1,2,3and
7days,andthereafteratweeklyintervalsfor
12weeks.

70. Sedimentationvolumewascalculated
accordingtotheequation:
F=V
u/V
o
Where,F=sedimentationvolume
V
u=ultimateheightofsediment
V
o=initialheightoftotalsuspension

71. The stability of suspension depends on the
particle size of the dispersed phase.
Change in the particle size with reference to time
will provide useful information regarding the
stability of a suspension.
A change in particle size distribution and crystal
habit studied by
 microscopy
 coulter counter method

72. Rapidprocessingofphotomicrographsis
enhancedbyattachingPolaroidcameratothe
pieceofmonomolecularmicroscope.
By using this photo micrographs we can
determine the changes in physical properties
and stability of suspensions.

74. pH MEASUREMENT
VISUAL INSPECTION
With visual inspection, the ingredients and the
final products are carefully examined for
purity and for appearance .