Powder & Liquid dosage forms.pdf

Powder & Liquid dosage forms
Types of Powder
Advantages of Powder
Disadvantages of Powder
Advantages of Liquid dosage form

1. POWDER
&
LIQUID DOSAGE FORMS
Prepared by: Dr.Harshil M Patel, Assistant Professor
Dept. of Pharmaceutics, SNLPCP, UMRAKH.

2. POWDER
•Apowderisahomogeneousmixtureofmoreorlessfinelydivided
particleormaterialindryform.Itisasoliddosageformof
medicamentwhicharemeantforinternalandexternaluses.They
arepresentincrystallineandamorphousform.

3. ADVANTAGES
•Theyimpartflexibilitywithregardtoawideselectionofdrugs.
•Theyarestablewhencomparedtootherdosageforms.
•Theyshowrapidtherapeuticeffect.
•Easeinadministrationtoallcategoriesofpatients.
••Theyareeconomicalbecausetheydonotrequirespecialtechniqueormachinery.
Chancesofincompatibilityareless.

4. DISADVANTAGES
•Drugshavingbitter,nauseousandunpleasanttastecannotbedispensedin
powderedform.
•Deliquescentandhygroscopicdrugscannotbedispensedinpowderedform.
•Drugswhichgetaffectedbyatmosphericconditionsarenotsuitablefordispensingin
powderform.

5. GENERAL METHOD OF
PREPARATION
•Thecrystallinesubstancesarepowderedseparatelyandthenweightherequired
quantityofeachingredient.
•Mixallingredientsinascendingorderoftheirweight.Mixthoroughlytoobtain
homogeneousmixture.
•Weighrequirednumberofpowdersandwrapinthepapers.
•Thehygroscopicanddeliquescentandvolatilesubstancerequirestobedouble
wrapped.
•Theinnerwrappershouldbewaxpapersoastopreventvolatilization.

6. TYPES OF POWDERS
1.DividedPowders
a)SimplePowder
b)Compoundpowder
2.BulkPowder
a)Dusting Powder
b)Effervescent Powder
c)Dentifrices
d)Insufflations
e)Douche Powder
f)Snuffs

7. DIVIDED POWDER
(a)Simplepowder:
Containsonlyoneingredienteitherincrystallineorinamorphousform.Thenfinely
dividedpowderisweighedwrappedasindividualdose.
(b)Compoundpowder:
Containstwoormorethantwosubstanceswhicharemixedtogetherandthendivided
intoindividualdoses.

8. BULK POWDERS
•Powder supplied in bulk quantities are applied by the patient according to his need.
They are preferably provided in sifter type container.

9. DUSTING POWDER
•Apowderisusedonskintorelieveirritationorabsorbmoistureandtokeepskinsoft
andcomfortable.Dustingpowdersareusedexternallyforlocalapplicationnot
intendedforsystemicaction.Theyareappliedtovariouspartofbodyaslubricants,
protectants,absorbents,antiseptics,astringentandantiperspirant.
•Dustingpowdersalwaysshouldbedispensedinaveryfinestateofsubdivisionto
enhanceeffectivenessandminimizeirritation.
•Whennecessarytheymaybepassedthrough80,100,numbersieves.

10. CHARACTERISTICS OF
DUSTING POWDER
•Dustingpowdershouldbehomogeneousinnature.
•Itshouldhavenon-irritableproperty.
•ItshouldbeFreeflowing.
•Powdershouldhavegoodspreadability.
•Dustingpowdershouldhavegoodadsorptionandabsorptionproperty.
•Dustingpowderusuallycontainssubstancesaszincoxide,starch,magnesium,carbonate,
lightmagnesiumoxide,boricacid,talc,kaolin,etc.
•Dustingpowdershouldnotbeappliedtobrokenskin.

11. FORMULA
•Rx,
ZincOxide:20gm
SalicylicAcid:5gm
Starch:25gm
Talc:50gm
Labelling:FOREXTERNALUSEONLY.

12. EFFERVESCENT POWDER
•Theyarespeciallypreparedsoliddosageformofmedicamentmeantforinternal
use.Theycontainmedicament(API)mixedwithcitricacid,tartaricacidandsodium
bicarbonate.Saccharinemaybeaddedassweeteningagent.Beforeadministration
thedesiredquantityisdissolvedinwater,theacidandbicarbonatereacttogether
producingeffervescence(releasingCO2).Thismixtureshouldbetakenwhile
effervescing.

13. PREPARATION
1.Fusionmethod
2.Wetmethod
(a)Fusionmethod:Inthismethod,alltheingredientsareplacedinaporcelaindish
andkeptinwaterbath,theyreleaseswaterandthismoisturesupportstoproduce
ahardmass.Thismassispassedthrough20numbersieve.Granulesobtained
aredried(60°Cinoven).Thenthegranulesarecollectedandsievedagain.
Leadingtofinegranules.
(b)Wetmethod:Ingredientsarewetwithalcohol(non-aqueoussolvent)andfollowthe
sameprocedure.

14. FORMULA
•Rx,
SodiumBicarbonate:35gm
Citricacid:25gm
Tartaricacid:15gm
Anhydroussodiumcarbonate:25gm
Storage:Itshouldbepackedinwaxpaperanddoublywrapped.

15. HYGROSCOPIC POWDER
➢Hygroscopicsubstanceabsorbswaterfromtheatmosphere.Itmayabsorbenough
toclumptogether,butadeliquescentsubstanceabsorbssomuchwaterfromthe
atmospherethatitactuallyformsaliquid.
➢Deliquescence,theprocessbywhichasubstanceabsorbsmoisturefromthe
atmosphereuntilitdissolvesintheabsorbedwaterandformsasolution.
Deliquescenceoccurswhenthevapourpressureofthesolutionthatisformedisless
thanthepartialpressureofwatervapourintheair.

16. PROBLEM ENCOUNTERED IN
POWDER FORMULATION
➢VolatileSubstance:
✓Certainvegetablespowderscontainvolatileoils.Topreventthelossofvolatileoils,thesevegetable
drugsmustbepowderedlightlyinamortar.
✓Similarlythevolatilizationofsubstanceslikementhol,camphorandessentialoilsmaytakeplaceon
incorporationinpowders.
✓Thisispreventedoratleastminimizedbytheuseofdoublewrapping.Theninnerwrappershouldbeof
waxpaperandouterwrappermaybeofanythickpaper.

17. ➢Hygroscopic and Deliquescent Powder:
✓The powders which absorb moisture from the atmosphere are called hygroscopic powder. But certain
powder absorb moisture to such a great extent that they go into a solution and are called deliquescent
powder.
E.g. Ammonium Chloride, Iron and Ammonium citrate, pepsin, phenobarbitone etc.
✓Such substances are usually supplied in granular form in order to expose less surface area to the
atmosphere.
✓These powder should not be finely powder. Such powder should be double wrapped.

18. ➢Efflorescent Powder:
✓Some crystalline substances liberate water of crystallization to humid atmosphere or during
trituration and thus become wet or liquefy.
✓Example of such substance include caffeine, citric acid etc.
✓This difficulty may be overcome by using either corresponding anhydrous salt or be inert
substance may be mixed with efflorescent substance before incorporating with other
ingredients.

19. ➢EutecticMixtures:
✓Whentwoormoresubstancearemixedtogethertheyliquefyduetotheformationofanewcompound
whichhasalowermeltingpointthenroomtemperature.Suchsubstancearecalledaseutecticmixture.
✓Exampleofsuchsubstancesincludementhol,thymol,camphor,phenol,salol,aspirinetc.
❑Thesesubstancecanbedispensedbytwomethod:-
I.Dispenseasseparatesetofpowderwithdirectionsthatonesetofwhichkindshallbetakenasdose.
II.Anequalamountofanyofinertabsorbentlikemagnesiumcarbonate,lightmagnesiumoxide,kaolin,
starch,lactose,calciumphosphateetc.maybemixedwitheutecticsubstanceandwhenblended
togetherlightlywithspatulaonasheetofpaper.

20. ➢Liquids:
✓Incertainprescriptions,theliquidmedicamentsarealsoincorporatedindispensingpowders.Ifthe
quantityoftheliquidissmall,itmaybetrituratedwithanequalamountofpowder,thentherestofthe
ingredientsareincorporatedinsmallportionswithcontinuoustrituration.
✓Ifthequantitiesofliquidsarelargethenanabsorbentmustbeadded.
➢Explosivesubstance:
✓Whenanoxidizingsubstance,suchaspotassiumchlorateismixedwithreducingsubstance,suchas
tannicacid,therearechancesofviolentexplosionwhichleadstoseriousconsequences.

21. ➢PotentDrugs:
✓Thesubstanceshavingamaximumdoseoflessthan60mgandpoisonoussubstancesareregarded
aspotentdrugs.
✓Smallquantitiesofpotentdrugsshouldnotbeweighedondispensingbalance.Thepotentdrugis
trituratedwithsomediluentsuchaslactoseindefiniteproportiontomakeaweighablequantityforeach
powder.
➢GranularPowder:
✓Thesearecertainsolidmedicamentswhicharerequiredtobeadministeredorallyinlargedoses.They
cannotbeprescribedintabletsandcapsulebecausealargenumberofthemwillberequiredtotakeas
singledose,whichisnotpossible.
✓Thesemedicamentsaredifficulttodispenseassuchinpowderformbecauseofitsbitter,nauseousand
unpleasanttaste.

22. ➢Effervescentgranules:
✓Effervescentgranulesarethespeciallypreparedsoliddosageformofmedicament,meantforinternal
use.Theycontainamedicamentsmixedwithcitricacid,tartaricacidandsodiumbicarbonate.

23. MIXING OF POWDER
➢Thepowdermaybemixedbyanuoneofthefollowingmethods:
1.Spatulation
2.Trituration
3.Geometricdilution
4.Sifting
5.Tumbling

24. SPATULATION
✓Inthismethod,mixingofpowderisdonebythemovementofaspatulathroughoutthe
powderonapapersheetofapaperoraporcelaintile.
✓Themethodisveryusefulinmixing:
i.Smallamountofpowder.
ii.Solidsubstancethatliquefyorformeutecticmixtures,whenitcloseandprolongedcontact
withoneanothersinceverylittlecompressionorcompactresults.
✓Themethodisnotsuitableforlargequantitiesofpowdersorforpowdercontainingoneor
morepotentsubstancesbecausehomogenousblendingmaynotoccur.

25. TRITURATION
✓Itisusedbothtoreduceparticlesizeandmixedpowder.
✓Ifparticlesizereductionisdesiredalongwithmixingofpowders,aporcelainmortarwitha
roughinnersurfaceispreferredtoaglassmortarwithsmoothworkingsurface.
✓Aglassmortarmaybepreferredforchemicalsthatmaystrainaporcelainsurfaceandfor
simplemixtureofsubstanceswithoutspecialneedforcomminution.
✓Aglassmortarcleansmorereadilyafteruse.

26. GEOMETRIC DILUTION
✓Thismethodisusedwhenpotentsubstancearemixedwithlargeamountofdiluents.
✓Thepotentdrugisplaceduponanapproximatelyequalvolumeofthediluentinamortarand
substancesareslightlymixedbytrituration.
✓Asecondportionofdiluentsequalinvolumetothepowdermixtureinamortarisaddedandtrituration
isrepeated.
✓Theprocessiscontinued,addingdiluentequalinvolumetothemixtureinthemortarateachstep,until
allthediluentisincorporated.
✓ForExample,if100mgofpotentdrugisrequiredtobemixedwith900mgoflactose,thenaccording
togeometricdilution,thefollowingprocedureshouldbefollowed:-

27. GEOMETRIC DILUTION
100mgofpotentdrug+100mgoflactose=200mgofmixture
200mgofthemixture+200mgoflactose=400mgofmixture
400mgofthemixture+400mgoflactose=800mgofmixture
800mgofthemixture+remainingportionoflactose=1000mgofmixture

28. SIFTING
✓Thepowdersaremixedbypassingthroughsifters.Thisprocessresultsinalightfluffyproductsandis
generallynotacceptableforcorporationofpotentdrugsintoadiluentbase.

29. TUMBLING
✓Tumblingistheprocessofpowdermixinginalargecontainerrotatedbyanelectricmotor.
✓Theseblendersarewidelyemployedinindustryaslargevolumepowdermixture.

30. DENTIFRICES (TOOTH POWDER)
➢Dentifricesarebulkpowdersusedtocleanteeth.Theycontainasoapordetergent(forcleaningaction),
mildabrasiveandananticariogenicagentMildabrasioncanbeprovidedbyusingfinelyprecipitated
CalciumCarbonate,SodiumChloride,MagnesiumChlorideetc.
➢Astrongabrasivesubstanceshouldnotbeusedasitmaycausedamagetothetooth.Theyareapplied
withthehelpoftoothbrushforcleaningthesurfaceofteeth.
➢Formula
RX
For100gmtoothpowder
Hardsoap,finepowder-5gm
Precipitatedcalciumcarbonate-94gm
Saccharinesodium-2gm
Peppermintoil-4gm

31. INSUFFLATIONS
➢Thesearefinelydividedpowdersintroducedintobodycavitiessuchastheear,nose,throat,tooth
socketsandvagina.
➢Aninsufflatorsisemployedtoadministertheseproducts.Itspraysthepowderintoastreamoffinely
dividedparticlesalloverthesiteofapplication.
➢Pressureaerosolsalsohavebeenemployedasameansofadministeringinsufflations,especiallyfor
potentdrugs.

32. SNUFFS
➢Thesearefinelydividedsoliddosageformofmedicamentwhichareinhaledintonostrilsforits
antiseptic,bronchodilatoranddecongestionactions.Traditionally,itissniffedorinhaledlightlyaftera
pinchofsnuffiseitherplacedontothebacksurfaceofthehand,heldpinchedbetweenthumband
indexfinger,orheldbyaspeciallymade"snuffing"device.Snuffcomesinarangeoftextureand
moistness,fromveryfinetocoarse,andfromtoast(verydry)toverymoist.

33. LIQUID DOSAGE FORMS

34. LIQUID DOSAGE FORM
➢Theuseofliquidpharmaceuticalshasbeenjustifiedonthebasisofeaseofadministrationandrapid
andefficientabsorptionofdrug.
➢Dosageformsmeanteitherforinternal,externalorparenteralusemaybesub-classifiedinto
monophasicorbiphasicliquiddosageforms.Themonophasicliquiddosageformsconsistsofeither
trueorcolloidalsolutionsorsolubilizedsystem.
➢Alltheseconsistsofonlyasinglephaseandmayhaveeitheraqueousornon-aqueoussolventsasthe
base.
➢Biphasicdosageformsarerepresentedbyemulsionsandsuspensionsandconsistoftwoimmiscible
phases,thecontinuousphaseandthedispersedphase.Thecontinuousphaseinbothisaliquid,the
dispersedphaseinemulsionsisalsoaliquidwhileincaseofsuspensions,thedispersedphase
consistsofafinelydividedsolid.

35. COMPARISON OF CHARACTERISTICS OF VARIOUS
LIQUID DOSAGE FORMS

36. ADVANTAGES OF LIQUID DOSAGE FORMS
➢Thedrugismorereadilyavailableforabsorptionfromliquiddosageformsascomparedtosoliddosageform.Byprovidingthe
druginsolution,thedissolutionphaseoftheabsorptionprocesscanbesurpassed,providingfastertherapeuticresponse.
➢Thedosesofdrugscanbeeasilyadjustedaccordingtotheneedofthepatient.Ifthedoseofactiveingredientistobealtered,
asimpleadjustmenttothequantityofsolutiontobetakenisallthatisrequired.
➢Liquidsareeasiertoswallowthantabletsorcapsulesandarethereforeespeciallysuitableforchildren,elderly,intensivecare
andpsychiatricpatients.
➢Gastricirritationduetocertaindrugslikepotassiumchlorideandwhenadministeredasasoliddosageformisavoidedor
reducedonadministrationasaliquiddosageformbecauseoftheimmediatedilutionbygastriccontent.
➢Drugswithlargedosescanbeeasilyadministeredasliquiddosageform.
➢Distributionofdruginliquiddosageformsisbetterthansoliddosageforms.
➢Liquiddosageformsaremoreeconomicaltoproducethansoliddosageforms.
➢Liquiddosageformscanbedesignedtoadministervianumberofroutes.Parenteralpreparations,douchesforvaginaluse,
cutaneous(foruseonskin)preparationsandophthalmicpreparationscanallbeliquids.

37. DISADVANTAGES OF LIQUID DOSAGE FORMS
➢Drugsareusuallylessstableinliquiddosageformsascomparedtosoliddosageformsliketabletsand
capsules,particularlyiftheyaresusceptibletohydrolysis.
➢Liquids,especiallyaqueouspreparations,aresusceptibletomicrobialcontamination.
➢Maskingtheunpleasanttasteofadruginsolutionismoredifficultthanwhenthedrugisinasoliddosageform.
➢Liquidpreparationsareusuallybulkyandthereforeinconvenienttostoreandcarry.Liquiddosageformsare
alwaysmuchlargerandmorebulkythansolidformulations.Coupledwiththisisthefactthatpharmaceutical
liquidsarepackedinglassbottles,whicharepronetobreakage.
➢Administrationofthecorrectdoseislessprecisesinceitdependsontheabilityofthepatienttomeasurethe
correctdoseusingasuitablemeasuringdevicesuchasaspoonoradropper.
➢Measuringdeviceistobesuppliedtothepatientsforaccuratedoseadministration.Thiswillhavecost
implicationsandinadditionthecounsellingisrequiredforitsuse.
➢Suspensionsandemulsionshavetheaddeddrawbackthattheymustbethoroughlyshakentoallowaccurate
dosing.

38. EXCIPIENTS USED IN FORMULATION
OF LIQUID DOSAGE FORMS
1.SweeteningAgents
2.Viscositycontrollingagents
3.Buffers
4.Antioxidants
5.Flavours
6.Preservative

39. SWEETENING AGENTS
Sweetenersareindispensablecomponentsofmanyliquidoraldosageforms,especiallythosecontainingbitter
orotherunacceptabletastes.Infact,sweeteningagentsmaycompriselargeportionsofsolidcontentinmost
liquidoraldosageforms.Sweetenersareoftenclassifiedaseithernutritive(caloric)ornon-nutritive(non
caloric).Non-caloricsweeteningagentsarepreferredfordiabeticpatients,asingestiondoescauseincreasein
systemicglucoseconcentrations.Someofthemostcommonlyusedsweetenersincludesucrose,sorbitol,
mannitol,liquidglucose,honeymolasses,saccharin,aspartame,sucralose,andacesulphame-K.Thetypesand
concentrationsofsweetenersforcommonprescriptionliquidmedicationsarereportedbyHill,Flaitz,andFrost.
Sucroseisthemostwidelyusedsweetener,withalonghistoryofuse.Itisawhcrystallinepowdersolublein
waterandalcohol.Itinhibitsthegrowthofmicroorganismsinsolutionatsucroseconcentrationsabove65wt%
byreducingthewater-activitycoefficient.Officialsimplesyrupisan85%w/Vsolutionofsucroseinwater.During
thepreparationofsucrosesolution,careshouldbetakentoavoidcharringandcaramelizationcausedbyheat.
SucroseischemicallyandphysicallystableinthepHrangeof4.0-8.0.Itisfrequentlyusedinconjunctionwith
sorbitol,glycerin,andotherpolyols,whichreducesitstendencytocrystallize.

40. VISCOSITY CONTROLLING AGENTS
Itissometimesdesirabletoincreasetheviscosityofaliquid,eithertoserveasanadjunctforpalatabilityorto
improvepourability.Thiscanbeachievedbyincreasingthesugarconcentrationbyincorporatingviscosity
controllingagentssuchaspolyvinylpyrrolidoneorvariouscellulosicderivatives(e.g.,methylcelluloseorsodium
carboxymethylcellulose).ThesecompoundsformsolutionsinwaterthatarestableoverawidepHrange.
Methylcelluloseandcarboxymethylcelluloseareavailableinanumberofdifferentviscositygrades.
Carboxymethylcellulosemaybeusedinsolutionscontaininghighconcentrationsofalcohol(upto50%)without
precipitating.Itisprecipitated,however,asaninsolublesaltofanumberofmultivalentmetalionssuchasAT**,
Fe***andCat*.Methylcellulosepolymersdonotforminsolublesaltswithmetalions,butcanbesaltedoutof
solutionwhentheconcentrationofelectrolytesorotherdissolvedmaterialsexceedcertainlimits.Theselimits
mayvaryfromabout2to40%,dependingontheelectrolyteandthetypeofmethylcelluloseinvolved.

41. BUFFERS
Duringstorageofliquidpreparations,degradationoftheproduct,interactionswithcontainer
componentsordissolutionofgasesandvaporscauseschangeintheirpHlevel,whichcanbe
preventedbyadditionofbuffer.Asuitablebuffersystemshouldhaveadequatebuffercapacityto
maintainthepHleveloftheproduct.Commonlyusedbuffersystemsarephosphates,acetates,
citrates,andglutamates.AlthoughbuffersensurepHstability,thebuffersystemcanaffectother
propertiessuchassolubilityandstability.Theionicstrengthcontributionsofthebuffersystemscan
affectstability.Bufferscanalsoactadverselyasgeneralacidorgeneralbasecatalystsandcause
degradationofthedrugsubstance.Therefore,beforeselectinganybuffersystem,theeffectofbuffer
speciesshouldbestudied.

42. ANTIOXIDANTS
➢Variousdrugsinsolutionaresubjecttooxidativedegradation.Oxidationisdefinedasalossofelectronsfrom
acompoundleadingtochangeintheoxidationstateofthemolecule.Suchreactionsaremediatedbyfree
radicalsormolecularoxygen,andareoftencatalyzedbymetalions.Moreover,oxidationofteninvolvesthe
additionofoxygen(orotherelectronegativeatomslikehalogens)ortheremovalofhydrogen.Drugs
possessingfavorableoxidationpotentialareespeciallyvulnerabletodegradation.Agentswithanoxidation
potentiallowerthanthatofthedruginquestionarecalledantioxidants.
➢Additionally,certainpropertiesoftheselectedprimarypackaging(suchaspolymerdegradation,oxygen
transmissionrates,impurities,etc.)canreadilyleadtooxidationofdrugmoleculesinsolutionandhencemay
requiretheadditionofantioxidantstomaintainproductstability.Theyareaddedtosolutionsaloneorin
combinationwithachelatingagentorotherantioxidantsandfunctionbybeingpreferentiallyoxidizedand
graduallyconsumedorbyblockinganoxidativechainreactionwheretheyarenotconsumed.

43. FLAVOURS
➢Flavouringcanbedividedintotwomajorcategories:selectionandevaluation.Muchhasbeenwrittenonboth
phasesofpharmaceuticalflavoring,butselectionremainsatotallyempiricactivity.
➢Thefourbasictastesensationsaresalty,bitter,sweet,andsour.Somegeneralizationsconcerningthe
selectionofflavourstomaskspecifictypesoftastehavebeensuggestedbyJanovskyandbyWesley.
Taste Sensation Recommended Flavour
Salt Butterscotch, maple, apricot, peach, vanilla, wintergreen mint.
Bitter
Wild cherry, walnut, chocolate, mint combinations, passion fruit, mint
spice, anise.
Sweet Fruit and berry, vanilla.
Sour Citrus flavors, liqorice, root beer, raspberry.

44. PRESERVATIVE
➢Inrecentyears,adequatepreservationofliquidproductshasincreasedinimportance.Reportsofclinical
complicationsarisingfrommicrobialcontaminationoforalandtopicalproductshaveoriginatedinseveral
EuropeancountriesandtheUnitedStates.Numerousproductrecallsandtightenedregulatoryand
compendialimitshavere-emphasizedtheneedfordieformulatortocarefullyandthoroughlyconsiderall
aspectsofthepreservativesystemchosenforaparticularformula.Inadditiontopresentingahealthhazard
totheuser,microbialgrowthcancausemarkedeffectsonproductstability.
➢Numeroussourcesofcontaminationexist.Includingamongthesearerawmaterials,processingcontainers
andequipment,themanufacturingenvironmentoperators,packagingmaterials,andtheuser.Manufacturing
techniquestominimizemicrobialcontaminationarepresentedundertheheading"Manufacturing
Considerations."Theremainderofthissectiondealswithpreservativesystemsforliquidproducts.

45. ➢Anidealpreservativecanbequalitativelydefinedasonethatmeetsthefollowingthreecriteria:
1.Itmustbeeffectiveagainstabroadspectrumofmicroorganisms.
2.Itmustbephysically,chemicallyandmicrobiologicallystableforthelifetimeoftheproduct.
3.Itmustbenon-toxic,non-sensitizing,adequatelysoluble,compatiblewithotherformulationcomponents,and
acceptablewithrespecttotasteandodourattheconcentrationsused.

46. SOME PHARMACEUTICALLY USEFUL PRESERVATIVES

47. SOLUBILITY ENHANCEMENT
TECHNIQUES
1.Solubilization
2.Co-solvency
3.pHmodification
4.Complexation
5.Hydrotrophy
6.Chemicalmodification

48. SOLUBILIZATION
➢ThistechniquewasintroducedbyMcBainin1937.Itisthedissolutionofpoorlysolublesolutemoleculesin
waterinpresenceofsurfactantsandformsthermodynamicallystablesolution.
➢Theprocessofdissolutioninpresenceofsurfactantshavebeendescribedastheformationofmicelles,which
enhancesthesolubilityofpoorlysolublesolute,whensurfactantofproperHLBisaddedinlowconcentration
toliquid,ittendstoorientatair-Liquidinterface.

49. ➢Ifsurfactantiscontinuedtobeaddedinhigherconcentration,air-liquidinterfaceisfullyoccupied(FigureB).
Atstillhigherconcentrations,thesurfactantmoleculesorionsareforcedtogointobulkofliquid,whenthe
particularconcentrationofsurfactantmoleculesismaintainedinthesystem,aggregatesofsurfactantsare
formedcallmicelles.(FigureC).
➢Theconcentrationofsurfactantatwhichmicellesformationtakesplaceiscalledcriticalmicelleconcentration
(CMC).Micellesmaybeofvariousshapeslike;spherical,rodorlamellar.Micelleformationincreasesthe
solubilityofasolutebyvirtureofitsdissolvinginorbeingabsorbedontothemicelle.
➢Solubilityenhancementofcresolsolutionwithsoapsolutionisaverygoodexampleofthistechnique.As
suchcresolhasonly2%v/vsolubilityinwaterbutwithsoapsolutionwecandissolveupto50%v/vcresolin
water(LysolSolution).

50. Figure: Limellar Micelle solubilizes the cresol in Water
➢ThistechniqueisusefultosolubilizemaywaterinsolublevitaminslikeA,DandKandtoprepare
solutionsofchloroxylenolandHexachlorophene.

51. CO-SOLVENCY
➢Co-solvencyisthetechniqueofincreasingthesolubilityofpoorlysolubledrugsinaliquidbyadditionofa
solventmisciblewiththeliquidinwhichthedrugisalsohighlysoluble.Cosolventssuchasethanol,glycerol,
propyleneglycolorsorbitoldecreasestheinterfacialtensionoralterthedielectricconstantofthemediumand
increasesthesolubilityofweakelectrolytesandnon-polarmoleculesinwater.Example:Formulationof
Diazepaminjectionusingpropyleneglycolascosolvent.

52. pHMODIFICATION
➢Mostofthedrugsareeitherweakacidsorweakbases.Theaqueoussolubilityofaweakacidoraweakbase
isgreatlyinfluencedbythepHofthesolution.Hence,thesolubilityofdrugthatiseitheraweakbaseora
weakacidmaybealteredbyadjustingthepHofthesolution.Thesolubilityofaweakbasecanbeincreased
byloweringthepHofitssolutionwhereasthesolubilityofaweakacidcanbeimprovedbyincreasingthepH.
pHadjustmentforimprovingthesolubilitycanbeachievedintwoways:
(a)Saltformation.
(b)Additionofbufferstotheformulation.However,pHadjustmentsshouldbedonejudiciouslysinceother
factorssuchasstability,bioavailability,etc.canalsobeaffectedbyachangeinpH.

53. COMPLEXATION
➢Incertaincases,itmaybepossibletoincreasethesolubilityofapoorlysolubledrugbyallowingittointeract
withasolublematerialformasolubleintermolecularcomplex.Itishoweveressentialthatthecomplexformed
iseasilyreversiblesothatthefreedrugisreleasedreadilyduringorbeforecontactwithbiologicalfluids.A
numberofcompounds,suchasnicotinamideandBeta-cyclodextrin,havebeeninvestigatedaspossible
agentstoincreasethesolubilityofwaterinsolubledrugs.
➢e.g.InteractionofIodinewithPovidonetoformwatersolublecomplexandpreparationofItraconazole
injectionbyforminginclusioncomplexofitraconazolewithhydroxypropylbetacyclodextrin.

54. HYDROTROPHY
➢Whenthesolubilityofdrugisenhancedowingtothepresenceoflargeamountofadditives,thetechniqueisreferredas
Hydrotrophy.Mechanismofthistechniqueisnotknownbuthasbeenspeculatedthatthischangeinthesolubilityofdrugin
solutionmightbeduetoeithersolubilization,complextationorchangeinthesolventcharacter.
➢Averygoodexampleofthistechniqueistheenhancementofcaffeinesolubilityinwaterduetopresenceoflarge
concentrationofsodiumbenzoate.
➢Otherexampleincludesolubilizationofbenzoicacidwithsodiumbenzoateandoftheophyllinewithsodiumacetateand
sodiumglycinate.
➢Thistechniqueishardlyusefulinpracticalsinceitrequireslargeamountofadditivestoshowmodestincreaseinthe
solubility.

55. CHEMICAL MODIFICTION
➢Solubilityofasubstancecanbeimprovedbychemicallymodifyingthesubstance.For
example,aqueoussolubilitycanbeimprovedbyincreasingthenumberofpolargroupsina
molecule.Thisisoftenachievedbysaltformation;forinstance,alkaloidsarepoorlysolublein
waterwhereasalkaloidalsaltsarefreelysolubleinit.Alternatively,amoleculemaybe
modifiedtoproduceanewchemicalentityorprodrug.Theaqueoussolubilityof
chloramphenicolsodiumsuccinate,forexample,isabout400timesgreaterthanthatof
chloramphenicol.Prodrugs,however,mustreverttoparentmoleculeafteradministration.