Topic 6- Suspensions

8/15/2019 Topic 6- Suspensions

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Suspensions

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suspensions

•

A suspension: is a disperse system in whichone substance (the disperse phase) isdistributed in particulate form throughoutanother (the continuous phase) (i.e. at least2 phases).

• According to the particle size of thedispersed phase, suspensions are dividedinto: Coarse suspension: which is a dispersion of

particles with a mean diameter greater than !m. Colloidal suspension is a dispersion of particles

with a mean diameter less than !m.

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"harmaceutical application of suspensions#hy suspensions$

Against solid dosage forms:•%f patient has a di&culty of swallowing solid dosageforms (a need for oral li'uid dosage form).

•aster rate of dissolution and oral absorption than

solid dosage forms, yet slower than solutions.

•ul*y insoluble powders as *aolin or chal* are betterformulated as suspensions so that they are easier tota*e.

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"harmaceutical application of suspensions#hy suspensions$

Against solutions:

•+rugs that have very low solubility are usefully formulated assuspensions.

•+rugs that have an unpleasant taste in their soluble forms(e.g., chloramphenicol (soluble) vs. chloramphenicol palmitate

(insoluble )).•"rolongation of eect (e.g. %.- and .C. suspensions).

•tability and instability issues:

%nsoluble forms of drugs may prolong the action of a drug bypreventing rapid degradation of the drug in the presence of

water (e.g., /0ytetracycline hydrochloride (soluble, hydrolysesrapidly) vs o0ytetracycline calcium salt (insoluble, stable).

1ona'ueous suspensions (tetracycline hydrochloride incoconut oil)

3econstitution (ampicillin suspension).06/06/16 BA-FP-JU-C


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Properties of a good pharmaceuticalsuspension

•

4here is ready redispersion of any sedimentwhich accumulates on storage.

• After gentle sha*ing, the medicament staysin suspension long enough for a dose to be

accurately measured.

• 4he suspension is pourable.

• "articles in suspension are small and

relatively uniform in size. so that theproduct is free from a gritty te0ture.

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ormulation of suspensionsormulation problems

. edimentation.2. 4hermodynamic instability.

5. #etting.

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Sedimentation

• 4he factors aecting the rate of sedimentation are in to*es6 e'uation:

• #here v7 velocity of sedimentation of a spherical particle of radius r,and density 8, in a li'uid of density 9, and viscosity , and where g isthe acceleration due to gravity.

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Thermodynamic instability

• %nterfacial free energy (%;).• %; 7 %nterfacial tension < surface area• locculation• Aggregation

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Flocculation

4he natural tendency of particles towards aggregation willdetermine the properties of a suspension. #hether or not asuspension is =occulated or de=occulated depends on the relative

magnitude of repulsive>attractive forces between particles.• +e=occulated suspension: the dispersed solid particles remain

separate and settle slowly. ?owever, the sediment that eventuallyforms is hard to redisperse and is described as a 6ca*e6 or clay.

• locculated suspension, individual particles aggregate into clumps

or =occules in suspension. ecause these =ocs are larger thanindividual particles, sedimentation is more rapid, but the sedimentis loose and easily redispersible. ;0cess =occulation may prevent6pourability6 due to its eect on rheological properties.

4he ideal is to use either a de=occulated system with a su&cientlyhigh viscosity to prevent sedimentation, or controlled =occulationwith a suitable combination of rate of sedimentation, type ofsediment and pourability.

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4he insoluble medicament may be :• +iusible solids (dispersible solids): 4hese are insoluble

solids that are light and easily wetted by water. 4hey mi0readily with water, and stay dispersed long enough for anade'uate dose to be measured. After settling theyredisperse easily. ;0amples include magnesium trisilicate,light magnesium carbonate, bismuth carbonate and light*aolin.

• %ndiusible solids: -ost insoluble solids are not easilywetted, and some particles may form large porous clumpsin the li'uid, whereas others may remain on the surface. 4hese solids will not remain evenly distributed in the

vehicle long enough for an ade'uate dose to bemeasured. 4hey may not redisperse easily. ;0amples forinternal use includes aspirin, phenobarbital, sulfadirnidineand chal*, and for e0ternal use calamine, hydrocortisone,suphur and zinc o0ide.

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Wetting


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Wetting

• ecause of the high interfacial tension between

indiusible solids and water@ air may be trapped in thesepoorly wetted particles which causes them to =oat to the

surface of the preparation and prevents them from being

readily dispersed throughout the vehicle.

• #etting of the particles can be encouraged by reducing

the interfacial tension between the solid and the vehicle,

so that adsorbed air is displaced from solid surfaces by

li'uid.

• uitable wetting agents have this eect, but decrease

interparticular forces thereby aecting =occulation.

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Wetting

Wetting agents:

?ydrophilic colloids such as acacia and tragacanth can act

as wetting agents. ?owever, care should be ta*en when

using these agents as they can promote de=occulation.

%ntermediate ? (hydrophiliclipophilic balance) surfactants

such as polysorbates (tweens) and sorbitan esters (spans)

are used for internal preparations. odium lauryl sulphate

and 'uillaia tincture are used in e0ternal preparations.

olvents such as ethanol, glycerol and the glycols alsofacilitate wetting.

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Suspending agents

• uspending agents increase the viscosity of the vehicle,

thereby slowing down sedimentation.

• -ost agents can form thi0otropic gels which aresemisolid on standing, but =ow readily after sha*ing.

• Care must be ta*en when selecting a suspending agentfor oral preparations.

•

uspending agents can be divided into Bve broadcategories: natural polysaccharides, semisyntheticpolysaccharides, clays, synthetic thic*eners andmiscellaneous compounds.

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uspending agentsNatural polysaccharides

• 4he main problem with these agents is their natural variability

between batches and microbial contamination.• 4hese materials should not be used e0ternally as they leave a

stic*y feel on the s*in.

• 4hey include tragacanth, acacia gum, starch, agar, guar gum,carrageenan and sodium alginate.

• 4ragacanth:

%s a widely used suspending agent and is less viscous at p? D.E.

As a rule: F.2g tragacanth powder is added per FF msuspension or 2g compound tragacanth powder per FF m

suspension. Compound 4ragacanth "owder " GHF containstragacanth, acacia, starch and sucrose and so is easier to use.

4ragacanth powder re'uires to be dispersed with the insolublepowders before water is added to prevent clumping .

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uspending agentsSemi-synthetic polysaccharides

• 4hese are derived from the naturally occurringpolysaccharide cellulose.

• ;0amples include

-ethylcellulose (Cologel I, CelacolI)

?ydro0yethylcellulose (1atrosol 2EFI)

odium carbo0ymethylcellulose (CarmellosesodiumI)

-icrocrystalline cellulose (AvicelI).

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uspending agentsClays

• 4hese are naturally occurringinorganic materials which are mainlyhydrated silicates.

• ;0amples include bentonite andmagnesium aluminium silicate(JeegumI).

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di t


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uspending agents

Synthetic thickeners:

• 4hese were introduced to overcome the variable'uality of natural products.

•;0amples include:

Carbomer (Carbo0yvinyl polymer, CarbopolI),

Colloidal silicon dio0ide (AerosilI, CabosilI)"olyvinyl alcohol ("JA).

Miscellaneous thickeners:

• Kelatin used as a suspending agent and a viscosityincreasing agent

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Preservation of a suspension

• #ater is the most common source of microbial

contamination.• Also the naturally occurring additives such as acacia and

tragacanth may be sources of microbes and spores.

• "reservative action may be diminished because ofadsorption of the preservative onto solid particles of drug,

or interaction with suspending agents.• Lseful preservatives in e0temporaneous preparations

include chloroform water, benzoic acid andhydro0ybenzoates.

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ormulation of suspension

. Control particle size. /n a small scale.

this can be done using a mortar andpestle. to grind down ingredients to aBne powder.

2. Lse a thic*ening agent to increaseviscosity of vehicle by using suspendingor viscosityincreasing agents.

5. Lse a wetting agent.

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The dispensing of suspensions

-ethod of preparation

A. Crystalline and granular solids areBnely powdered in the mortar. 4hesuspending agent should then be

added and mi0ed thoroughly in themortar. Avoid gumming or ca*ing.

. Kradual addition of vehicle, ma*e a

paste then continue till becomesmooth and pourable, rinse and up tovolume in a tared bottle.

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!ariations:

•%f wetting agents are included in the formulation,add them before forming the paste.

•%f syrup and>or glycerol are in the formulation,use this rather than water to form the initial

paste.•%f soluble solids are being used, dissolve them inthe vehicle before or after ma*ing the paste.

•eave addition of volatile components,

colourings or concentrated =avouring tincturessuch as chloroform spirit, li'uid li'uorice e0tractand compound tartrazine solution until near theend.

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The dispensing of suspensions


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Preparation of suspension fromoral solid dosage form

• 4he tablet will be crushed or capsule contentsemptied into the mortar and a suspending agentadded.

• A paste is formed with the vehicle and then

diluted to a suitable volume, with the additionany other desired ingredients such aspreservative or =avour.

• A short e0piry of no more than 2 wee*s (more

li*ely to be D days) should be given owing to thelac* of *nowledge about the stability of theformulation.

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P ti f i f


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Preparation of suspension fromdry po"ders and granules for

reconstitution• 3econstitution because of chemical or

physical instability.

• oosening of powder from bottom of thecontainer.

• 4he speciBed amount of cold, puriBed watershould then be added, sometimes in two ormore portions with sha*ing.

• some preparations may be preparedimmediately before ta*ing from individuallypac*ed sachets of powder or from bul*solids.

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Containers for suspension

• uspensions should be pac*ed in amberbottles, plain for internal use and ribbed fore0ternal use.

• 4here should be ade'uate air space above

the li'uid to allow sha*ing and ease ofpouring.

• A E m medicine spoon or oral syringeshould be given when the suspension is for

oral use.

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Special label and advice for


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Special label and advice forsuspension

• 4he most important additional label for

suspensions is 6Shake well before use6,• Store in a cool place. tability of

suspensions may be adversely aected byboth e0tremes and variations of temperature.

• ome suspensions. such as those made fromreconstituting dry powders, may need to bestored in a refrigerator.

•

;0temporaneously prepared and reconstitutedare re'uired to be recently or freshlyprepared, with a wee* e0piry date.

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EFml Maolin and -orphine -i0ture ".

-aster formulaEFml

ight *aolin 2g5Fg

odium bicarbonate EFFmg D.Eg

Chloroform and

morphine tincture F.mlNml

#ater to Fml toEFml

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Chal* -i0ture, "aediatric ". -itteFFml

-aster formula FFml

Chal* FFmg 2g

4ragacanth Fmg 2FFmg

yrup F.Eml Fml

Concentrated cinnamon

water F.F2ml F.ml

+ouble strength chloroform

water 2.Eml EFml

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Spironolactone suspension 15mg/5ml. Sig.5ml

t.d.s. itte 100ml. For a !-"ear-old c#ild.

-aster formula FFml

pironolactone '.s.< 5FFmg

Compound orange spirit F.2OF.2mlCologel 2FO 2Fml

#ater to FFO FFml


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-enthol and ;ucalyptus %nhalation " GHF.-itte FFml

-aster formula

-enthol 2g

;ucalyptus oil Fml

ight magnesium carbonate Dg

#ater to FFml

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2FFml Calamine otion "

-aster formula 2FFml

Calamine Eg 5Fg

Pinc o0ide Eg Fg

entonite 5g Ng

odium citrate EFFmg g

i'uiBed phenol F.Eml ml

Klycerol Eml Fml#ater to FFml to 2FFml

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Mey points

• uspensions can be used to administer

an insoluble solid by the oral route.• uspensions may be used to replace

tablets, to improve dissolution rate, toprolong action and to mas* a bad taste.

•

olids may be diusible or indiusibleand re'uire dierent dispensingtechni'ues.

• to*es6 e'uation can be applied whenformulating a suspension to help ensureaccurate dosage of the drug.

• locculated particles settle 'uic*ly andredisperse easily, whilst de=occulatedparticles settle slowly but tend to ca*e.

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Mey points

• ?ydrophobic solids may re'uire wetting

agents.• uspending agents are added to slow down

the rate of settling of the solid.• uspending agents may be natural

polysaccharides, semi syntheticpolysaccharides, clays or synthetic polymers.

• ome suspensions are made by addingwater to reconstitute manufactured powderswhen stability is a problem.

•

ha*e well before use6 and 6tore in a coolplaceQ should be part of the labels on asuspension.

• %nhalations are suspensions of a volatilematerial adsorbed onto a diusible solid.

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Topic 6- Suspensions

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