Suspension

SuspensionSuspension

Rachmat MauludinRachmat Mauludin

IntroductionIntroduction Suspension is a disperse system in which one Suspension is a disperse system in which one

substance (dispersed phase) is distributed in substance (dispersed phase) is distributed in particulate form throughout another (the particulate form throughout another (the continuous phase)continuous phase)

Contain one or more insoluble medicaments in a Contain one or more insoluble medicaments in a vehicle with other additives such as stabilizer, vehicle with other additives such as stabilizer, preservativespreservatives

Used for oral administration, inhalation, topical Used for oral administration, inhalation, topical application, as ophthalmic preparation, for application, as ophthalmic preparation, for parenteral administration and as aerosolparenteral administration and as aerosol

Colloidal suspension: dispersed particles <1Colloidal suspension: dispersed particles <1μμmm Coarse suspension : Coarse suspension : dispersed particles >1dispersed particles >1μμmm

SuspensionSuspension

Colloidal suspension

Pharmaceutical applicationPharmaceutical application

Drugs have very low solubility are usefully Drugs have very low solubility are usefully formulated as suspensionformulated as suspension

People have difficulty swallowing solidPeople have difficulty swallowing solid Unpleasant taste in their soluble form formulated Unpleasant taste in their soluble form formulated

as suspension more palatable as suspension more palatable Chloramphenicol chloramphenicol palmitat Chloramphenicol chloramphenicol palmitat suspensionsuspension

Optimal dissolution occurs immediately than Optimal dissolution occurs immediately than solid formulationsolid formulation

Insoluble forms of drug may prolong the action Insoluble forms of drug may prolong the action of drugs (preventing rapid degradation of drugs (preventing rapid degradation oxytetracycline)oxytetracycline)

Unstable drug when contact vehicle should Unstable drug when contact vehicle should prepared immediately (ampicillin)prepared immediately (ampicillin)

Drug unstable in water my be suspended in non-Drug unstable in water my be suspended in non-aqueous phase (oil), tetracycline for ophthalmic aqueous phase (oil), tetracycline for ophthalmic useuse

In solid; Bulky, in suspension; Easier to take, for In solid; Bulky, in suspension; Easier to take, for example kaolin or chalk, magnesium trisilicate example kaolin or chalk, magnesium trisilicate BP antacidBP antacid

Intramuscular, intra-articular or subcutaneous Intramuscular, intra-articular or subcutaneous injection formulated as suspensioninjection formulated as suspension

Lotion formulated to leave a thin coating of Lotion formulated to leave a thin coating of medicament on skin (calamine lotion BPA)medicament on skin (calamine lotion BPA)

Pharmaceutical applicationPharmaceutical application

A Good suspensionA Good suspension

Ready dispersion of any sediment which Ready dispersion of any sediment which accumulates on storageaccumulates on storage

Medicaments stays in suspension long Medicaments stays in suspension long enough for a dose to be accurately measuredenough for a dose to be accurately measured

Suspension is pourableSuspension is pourable Particles in suspension are small and Particles in suspension are small and

relatively uniform, so that free from a gritty relatively uniform, so that free from a gritty texturetexture

Ensure a good Ensure a good suspensionsuspension1.1. Control particle size, grind down the Control particle size, grind down the

particles to a fine powders and sievedparticles to a fine powders and sieved

2.2. Increase viscosity by thickening agentIncrease viscosity by thickening agent

3.3. Use wetting agent:Use wetting agent:• Diffusible solid (easily wetted by water): Diffusible solid (easily wetted by water):

magnesium carbonate, light kaolinmagnesium carbonate, light kaolin• Indiffusible solid (form large porous clump):Indiffusible solid (form large porous clump):

aspirin, phenobarbital, chalk, calamine, aspirin, phenobarbital, chalk, calamine, hydrocortisone, sulphur and zinc oxidehydrocortisone, sulphur and zinc oxide

Problem encounteredProblem encountered Sedimentation, rate of sedimentationSedimentation, rate of sedimentation

Flocculation:Flocculation:a deflocculated suspensiona deflocculated suspension, dispersed solid , dispersed solid particles remain separate and settle slowly.particles remain separate and settle slowly.sediment forms a cake or clay, sediment forms a cake or clay, a deflocculated a deflocculated suspensionsuspension needs sufficiently high viscosity to needs sufficiently high viscosity to prevent sedimentation or controlled flocculationprevent sedimentation or controlled flocculationa flocculated suspensiona flocculated suspension, individual particles , individual particles aggregate into clump or floccules in suspensionaggregate into clump or floccules in suspension

9

)(2 2 gr

Problem encounteredProblem encountered Wetting, encouraged by reducing the interfacial Wetting, encouraged by reducing the interfacial

tension between the solid and vehicles using tension between the solid and vehicles using wetting agent (surfactant, hydrophilic colloid)wetting agent (surfactant, hydrophilic colloid)

Wetting agent:Wetting agent:

internal used: surfactant polysorbates and internal used: surfactant polysorbates and sorbitan ester, glycerol, glycolssorbitan ester, glycerol, glycols

external used: sodium lauryl sulphate,external used: sodium lauryl sulphate,

Quaillaia tincture Quaillaia tincture

Suspending agentSuspending agent

Increase the viscosity of the vehicle, thereby Increase the viscosity of the vehicle, thereby slowing down sedimentationslowing down sedimentation

Mostly can form thixotropic gels, semisolid on Mostly can form thixotropic gels, semisolid on standing but flow readily after shaking.standing but flow readily after shaking.

Selected suspending agent for oralSelected suspending agent for oral Acid environment alter physical characteristicAcid environment alter physical characteristic Bind certain medicaments, less bioavailabilityBind certain medicaments, less bioavailability

1.1. Natural polysaccharide Natural polysaccharide problem; microbial contaminationproblem; microbial contaminationTragacanth: less viscous at pH 4-7.5Tragacanth: less viscous at pH 4-7.5used 2%, used 2%, Tragacanth powder BP: Tragacanth, acacia, Tragacanth powder BP: Tragacanth, acacia, starch, sucrosestarch, sucroseagar, guar gum, carageenan and sodium agar, guar gum, carageenan and sodium alginatealginateNot for external used, sticky onto skinNot for external used, sticky onto skin

Suspending agentSuspending agent

2.2. Semisynthetic polysaccharide Semisynthetic polysaccharide Methylcelloluse, HPMC Methylcelloluse, HPMC (Hydroxypropilmethylcelloluse), (Hydroxypropilmethylcelloluse), NaCMC, microcrystal cellulose (avicel)NaCMC, microcrystal cellulose (avicel)

3.3. Clays: bentonite magma, veegumClays: bentonite magma, veegum4.4. Synthetic thickener: Carbopol, Aerosil, Synthetic thickener: Carbopol, Aerosil,

polyvinyl alcoholpolyvinyl alcohol5.5. Miscellaneous: Gelatin Miscellaneous: Gelatin

Suspending agentSuspending agent

PreservationPreservation

Water source of microbial contaminantWater source of microbial contaminant

Diminished because of adsorption onto Diminished because of adsorption onto surface particle (thickening agent)surface particle (thickening agent)

Ex: chloroform water, benzoic acid, Ex: chloroform water, benzoic acid, hydroxybenzoates hydroxybenzoates

DispensingDispensing

1.1. Crystalline and granular are finely Crystalline and granular are finely powdered in the mortalpowdered in the mortaladded suspending agent and mixedadded suspending agent and mixeddon’t to much pressure (caking) and heat don’t to much pressure (caking) and heat and friction make it sticky and friction make it sticky

2.2. Added a little liquid vehicle, mix well until Added a little liquid vehicle, mix well until smooth and free of lumpssmooth and free of lumpscontinue water adding till can be pouredcontinue water adding till can be pouredfurther water to rinse all the powder into further water to rinse all the powder into bottle, made up to volume.bottle, made up to volume.

DispensingDispensing

3.3. Crush the tablets to fine powders, if a Crush the tablets to fine powders, if a fractional tablet: fractional tablet:

Determine the average weight of a tablet, Determine the average weight of a tablet, determine amount the crushed tablet with determine amount the crushed tablet with compared-calculationcompared-calculation

Some pharmacist is recommend that Some pharmacist is recommend that suspension be homogenized for maximum suspension be homogenized for maximum uniformity and improved physical stabilityuniformity and improved physical stability

DispensingDispensing

VariationVariation Wetting agent are include, added before Wetting agent are include, added before

forming pasteforming paste Syrup and glycerol used to form pasteSyrup and glycerol used to form paste Soluble solid dissolve in the vehicle Soluble solid dissolve in the vehicle

before or after making the pastebefore or after making the paste Leave addition of volatile component or Leave addition of volatile component or

concentrated tincture until near the endconcentrated tincture until near the end

DispensingDispensing

Powder Paste Suspension

Vehicle/water Vehicle/water

Wetting agent Sugar/Glycerol

Preparation from dry Preparation from dry powderpowder Loosened from bottom of bottle by tappingLoosened from bottom of bottle by tapping

Two more portion water addition, shaking Two more portion water addition, shaking until suspended until suspended

Prepare immediately before taking from Prepare immediately before taking from individually packed sachet individually packed sachet

Container and labelsContainer and labels

Amber bottle, plain for internal and ribbed for Amber bottle, plain for internal and ribbed for externalexternal

A 5 ml medicine spoon or oral syringe provided A 5 ml medicine spoon or oral syringe provided ““Shake well before used”Shake well before used” ““Store in a cool place”Store in a cool place” Reconstituted suspension has short shelf life, Reconstituted suspension has short shelf life,

freshly prepared, with 1-4 weeks expiry datefreshly prepared, with 1-4 weeks expiry date

InhalationInhalation

Volatile component are adsorbed onto Volatile component are adsorbed onto surface of diffusible solid to unsure surface of diffusible solid to unsure uniform dispersionuniform dispersion

Addition hot water will evaporate volatile Addition hot water will evaporate volatile oiloil

1 g light magnesium carbonate for each 1 g light magnesium carbonate for each 2 ml volatile oil (eucalyptus oil) or 2 g 2 ml volatile oil (eucalyptus oil) or 2 g volatile solid (such as menthol) volatile solid (such as menthol)

PrescribePrescribe

Preparation 18.1Preparation 18.1

Dissolve sodium bicarbonate in 100ml waterDissolve sodium bicarbonate in 100ml water Kaolin placed in mortal and added sodium Kaolin placed in mortal and added sodium

bicarbonate solutionbicarbonate solution Add chloroform and tinctureAdd chloroform and tincture Poured into bottle and make up to volume Poured into bottle and make up to volume

PrescribePrescribe

Preparation 18.2Preparation 18.2

Chalk and Tragacanth mixed in mortalChalk and Tragacanth mixed in mortal Added Syrup to make pasteAdded Syrup to make paste Added chloroform followed cinnamon Added chloroform followed cinnamon

waterwater Poured into tarred 100 ml bottlePoured into tarred 100 ml bottle Make up to volumeMake up to volume

Prescribe Prescribe

Preparation 18.3Preparation 18.3

Spironolactone tablet crushed in mortal Spironolactone tablet crushed in mortal or weight powder into mortalor weight powder into mortal

Add cologel and mixed to a pasteAdd cologel and mixed to a paste Add gradually water and followed orange Add gradually water and followed orange

spiritspirit Poured to tared bottle make up to volumePoured to tared bottle make up to volume

PrescribePrescribe

Prescribe Prescribe

Preparation 18.4Preparation 18.4

Grinded menthol and dissolved in Grinded menthol and dissolved in eucalyptus oileucalyptus oil

Added gradually magnesium carbonateAdded gradually magnesium carbonate Added a part of water and poured to Added a part of water and poured to

tared bottletared bottle Make up to volumeMake up to volume

PreparationPreparation

Dry powders weighed and mixed in Dry powders weighed and mixed in mortarmortar

Adding glycerol to powdersAdding glycerol to powders Sodium citrate dissolved in water and Sodium citrate dissolved in water and

gradually added to mixture to form pastegradually added to mixture to form paste Added liquid phenol to pasteAdded liquid phenol to paste Poured to a bottle and make up to Poured to a bottle and make up to

volumevolume

LabelLabel

PreparationPreparation Calamine and Hidrocortisone mixed Calamine and Hidrocortisone mixed

geometricallygeometrically Dissolved menthol in IPADissolved menthol in IPA Mixture powders added to Menthol-IPA Mixture powders added to Menthol-IPA

until form pasteuntil form paste Gradually add 40 ml cetaphil in small Gradually add 40 ml cetaphil in small

portion of mixture with triturationportion of mixture with trituration Combine the rest paste to cetaphil Combine the rest paste to cetaphil

mixturemixture Make up to volumeMake up to volume