aerosol formulation

1. TOPIC: AEROSOL
SUBMITTED BY: MADIHA DURRANI

2. AEROSOL:
Aerosol orpressurizedpackage isdefinedas“a systemthatdependsonthe powerof compressedgasor
liquefiedgastoexpel the contentfromthe container”
 Pharmaceutical aerosol isdefinedas aerosol productcontainingactive ingredientsdissolved,
suspendedoremulsifiedinapropellantormixture of solventandpropellantandintendedfor
oral or topical administrationorforadministrationintoeye,nose,ear,rectumandvagina.
 In 1942, firstaerosol wasdeveloped( insecticide)
 In 1950, pharmaceutical aerosol fortopical administrationwasdeveloped.
 In 1955, aerosol forlocal activityinthe respiratorytract was developed(epinephrine).
AEROSOL CHARACTERISTICS:
 Particle size distribution
 Uniformityof dose formeteredvalve
 Deliveryrate
 Wetnessandthe temperature of spray
 Spray pattern
 Velocityof spray
 Foam density
 Fluidviscosity
COMPONENTSOF AEROSOLS:
 Propellant
 Container
 Valve andactuator
 Productconcentrate
1. PROPELLANTS:
 Responsible fordevelopingproperpressure withinthe container.
 Provide drivingforce toexpelthe productfromthe container.
TYPES OF PROPELLENTS:
a) liquefiedgaspropellants
b) compressedgaspropellants
A) LIQUIFIED GASPROPELLANTS:
 Liquefiedpropellants are gasesthatexistsasliquidunderpressure.
 Because the aerosol isunderpressure propellantexistsmainlyasliquid,butitwill alsobe inthe
headspace as a gas
 The product isusedup as the valve isopened,some of the liquidpropellantturnstogas and
keepthe headspace full of gas

3.  In thiswaypressure remainsconstantandthe sprayperformance ismaintainedthrouoghtthe
life of aerosol.
CHLORO FLUORO CARBONS:
 Propellantof choice fororal and inhalation
ADVANTAGE: DISADVANTAGE:
 chemical inertness highcost
 Lack of toxicity it depletesthe ozone layer
 Non- flammability
 Lack of explosiveness
examples:
 trichloromonofluoromethane(propellant11)
 dichlorodifluoromethane(propellant12)
 dichlorotetraflouroethane (propellant114)
HYDROCARBONS:
 can be usedforwaterbasedaerosolsandtopical use.
ADVANTAGES DISADVANTAGES
 inexpensive inflammable
 excellentsolvents unknowntoxicityproduced
 it doesnotcause ozone depletion
examples:
 propane (propellantA- 108)
 isobutane (propellantA-31)
 butane (propellantA-17)
B) COMPRESSED GAS PROPELLANTS:
 compressedgaspropellantsoccupythe headspace above the liquid
 whenthe aerosol valve isopened,thatgaspushesthe liquidoutof the container
 the amountof gas inthe headspace remainsthe same butit has more space,and as a resultthe
pressure will dropduringthe lifeof can
 spray performance ismaintainedhoweverbycareful choice of aerosol valve andactuator.
2) CONTAINERS:
Theymust be able to withstandpressureashighas 140 to 180 psig(poundpersq.inch gauge) at1300
F,
differenttypesof aerosol containersare availableas:
A) METALS:
 tinplatedsteelcontainers

4.  aluminum
 stainlesssteel
B) GLASS:
 uncoatedglass
 plasticcoatedglass
TIN PLATED STEEL CONTAINERS:
 it consistsof a sheetof steel plate;thissheetis coatedwithtinbyelectrolyticprocess
 the coatedsheetiscut intothree pieces(top,bottomandbody)
 the top, bottomare attached to bodybysoldering
 whenrequireditiscoatedwithorganicmaterial usuallyoleoresin,phenolic,vinyl orepoxy
coating
 weldingeliminatessolderingprocess,savesconsiderablemanufacturingtime anddecreasesthe
productor containerinteraction
 recentdevelopmentsinweldinginclude sardonicsystemandconoweldsystem
ALUMINIUMCONTAINERS:
 usedforinhalationandtopical aerosols
 manufacturedbyimpactextrusionprocess
 lightinweight,lessfragile,lessincompatibilitydue toitsseamlessnature
 greaterresistance tocorrosion
 addedresistance canbe obtainedbycoatinginside of the containerwithorganiccoatinglikr
phenolic,vinyl orepoxyandpolyamide resins
STAINLESS STEEL CONTAINERS:
 usedforinhalationaerosols
 extremelystrong
 resistanttomany materials
 no needforinternal coating
 costly
C) VALVES:
 easyto openand close
 capable of deliveringthe contentinthe desiredformsuchasspray,foam, solidstreametc
 it can deliveragivenamountof medicament
TYPES OF VALVES:
 continuoussprayvalve
 meteringvalve

5. CONTINOUSSPRAY VALVE:
 usedfortopical aerosol
 consistsof,stem,valve bodyorhousing,diptube, gasket,spring,mountingcup
1. mountingcup:it can use to attach the valve withcontainer,andismade of tin- platedsteel,
aluminumandbrass.The underside of the valve cupiscoatedwithsingle ordouble epoxyorvinyl resins
2. valve bodyor housing:itismade up of nylonorberlinandcontainsan openingatthe pointof
attachmentof diptube (0.013- 0.080 inch)
3. stem:it ismade of nylonor berlin;brassandstainlesssteel canalsobe used.(orifice:0.013- 0.030
inch)
4. gasket:it ismade of neoprene rubber
5. spring:it ismade of stainlesssteel andusedtoholdgasketinplace.
6. dip tube:itismade of polyethyleneorpolypropylene;the innerdiameteris0.120- 0.125 inch.
However,forcapillarydiptube innerdiameteris0.050 inchand for highlyviscousproductsoutis0.195
inch.

6. METERING VALVE:
 usedfordispensingof potentmedications
 operatesonthe principle of achamberwhose size determinesthe amountof medications
dispensed
 approximately50- 150mg of liquidmaterial can be dispensedatone time withthe use of such
valves.
D) ACTUATORS:
 these are speciallydesignedbuttonswhichhelpsindeliveringthe drugindesiredformi.e spray,
wetstream,foamor solidstream
 actuators are of differenttypes:
1. SPRAY ACTUATORS:
 it can be usedfor topical preparation,suchasantiseptics,local anesthetics,andsprayon
bandages
 it allowsthe streamof productconcentrate andpropellanttopassthroughvariousopenings
and dispense asspray
2. FOAMACTUATORS:
 it consistsof large orifice whichrangesfrom0.070- 0.125 inch
3. SOLID STREAM ACTUATORS:
 these actuatorsare requiredfordispensingsemi- solidproductssuchasointments
4. SPECIAL ACTUATORS:
 these are usedforspecificpurpose
 it deliversthe medicamenttoappropriate site of actionsuchasthroat, nose,dental andeyes
FORMULATION OFAEROSOLS:
TYPES OF AEROSOL SYSTEMS:
The type of aerosol systemselecteddependson:
manufactre
concentrate
add
propellants
aerosols

7.  physical,chemical andpharmacological propertiesof drug
 site of application
A) SOLUTION SYSTEM:
 thissystemalsoreferredastwophase system, whichconsistsof vaporandliquidphase
 if active ingredientissolubleinpropellantnoothersolventisrequired
 the vapor pressure of systemisreducedbyadditionof lessvolatile solventsasethanol,acetone,
propylene glycol,glycerin,ethyl acetate.Thisresultsinproductionof largerparticlesupon
spraying
 the amountof propellantmayvaryfrom5% (forfoams) to 95% (for inhalations).
 Solutionaerosolsproducesfinetocoarse spray
 These are useful fortopical preparations
 Packagedinplasticcoatedglasscontainers
B) WATER BASED SYSTEMS:
 Larger amountsof water can be usedto replace all orpart of the non- aqueoussolventsusedin
aerosols
 Producessprayor foam
 To produce spray,formulationmustconsistof dispersionof active ingredientsandother
solventsinemulsionsysteminwhichthe propellantisinexternal phase
 Since propellantandwaterare notmiscible,athree phase aerosol form(propellant,waterand
vapor phase)
TYPES OF
AEROSOL
SYSTEMS
FOAM
SYSTEM
SOLUTION
SYSTEM
SUSPENSI
ON
SYSTEM
WATER
BASED
SYSTEM

8.  Ethanol can be usedas co- solventtosolubilize propellantinwater.Italsoreducesthe surface
tensionaidinginthe productionof smallerparticles
 0.5- 2% of surfactantsisusedto produce a homogenousdispersion
C) SUSPENSIONSYSTEM:
 It involvesdispersionof active ingredientsinthe propellantormixture of propellant
 To decrease the rate of settlingof dispersedparticles,surfactantsordispensingagentscanbe
added
 Primarilyusedforinhalational aerosols
D) FOAM SYSTEMS:
 Emulsionandfoamaerosolsconsistsof active ingredients,aqueousornon- aqueousvehicles,
surfactants,propellantsandare dispersedasa stable orquickbreakingfoamdependingonthe
nature of ingredientsandthe formulation.
MANUFACTURING OFPHARMACRUTICAL AEROSOLS:
A) PRESSURE FILLING:
ADVANTAGES:
 Contaminationdue tomoisture isless
 Highproductionspeedcanbe achieved
it consists of a pressure burette capable of metering
smaal volume of liquified gas into aerosol container
under pressure
the propellantisallowedtoflowwithitsownvapour
pressure inthe containerthroughaerosol valve
the trapedair escapesoutfromthe uppervalve
propellantstopflowingwhenthe pressure of burette and
containerbecomesequal
additional propellantmaybe addedbyincreasingthe
pressure infillingapparatusthroughthe use of compressed
gas

9. B) COLD FILLING:
C) COMPRESSED GASFILLING:
QUALITY CONTROL TESTS:
It includesthe testingof:
 Propellants
 Valves,actuators,anddiptubes
 Containers
 Weightchecking
 Leaktesting
 Spray testing
1. PROPELLANTS:
cool the product
concentrate to-
400F
fill intothe
cooledcontainer
add cool
propellant to
product
concentrate
compressedgasesare
presentunderhigh
pressure incylinders
these cylindersare fitted
withthe pressure reducing
valve anddeliveryguage
a flow indicatorisalso
present

10.  Vaporpressure anddensityof the propellantare determinedandcomparedwithspecification
sheets.
PARAMETER TESTED BY
 identification Gas chromatography
IR spectroscopy
 purityand acceptability Moisture,halogen
Non- volatile residuedeterminations
2. CONTAINERS:
 containersare examinedfordefectsinlining
 qualitycontrol aspectsinclude degree of conductivityof electriccurrentasmeasure of exposed
metals
 glasscontainersexaminedforflaws
3. WEIGHTCHEKING:
 isdone by periodicallyaddingtothe fillingline taredemptyaerosolcontainers,whichafter
fillingwithconcentrate are removedandweighed
 same procedure isusedforcheckingweightof propellantsbeingadded
4. LEAK TESTING:
 it isa meanof checkingcrimpingof the valve anddetectthe defective containersdue toleakage
 isdone by measuringthe crimpsdimensionandcomparing
 final testingof valve closure isdone bypassingthe filledcontainersthroughwaterbath
5. SPRAY TESTING:
 mostpharmaceutical aerosolsare 100% spray tested
 thisservestoclearthe diptube of pure propellantandpure concentrate
 to checkthe defectsinvalvesandspraypattern
EVALUATIONTESTS:
A) FLAMMABILITY AND COMBUSTABILITY:
 flashpoint
 flame projection
1. FLASH POINT:
Apparatus:tag ovencupapparatus
Productis chilledto -250
Fand testliquidtemperature canincrease slowlyandthe temperature atwhich
the vapor ignite iscalledasflashpoint
2. FLAME PROJECTION:
Productis sprayedfor4 secsintoa flame andflame isextended,exactlengthismeasuredwitharuler

11. B) PHYSICOCHEMICALCHARACTERISTICS:
PROPERTY METHOD
1. vapor pressure  pressure gauge
 can puncturingdevice
2. density  hydrometer
 pycnometer
3. moisture  Karl- Fischermethod
 gas chromatography
4. identificationof propellants  gas chromatography
 IR spectroscopy
C) PERFORMANCE:
1. AEROSOL VALVE DISCHARGE RATE:
 Contentsof the aerosol productisdischargedfoe specificperiodof time
 By reviewingthe containerafter time limitthe change inthe weightpertime dispensedgives
the discharge rate
2. SPRAY PATTERN:
 The methodisbasedon the impingementof sprayonpiece of paperthat has beentreatedwith
die,talcmixture.
 The particlesthatstrikesthe papercause the dye to gointo the solutionandtobe adsorbed
ontopaper givingarecord of spray forcomparisonpurpose
3. DOSAGE WITH METERED VALVE:
Reproducibilityof dosage canbe determinedby:
 Assaytechniques
 Accurate weighingof filledcontainerfollowedby dispensingof several doses,containersare
than reviewedanddifference inweightdividedbynumberof dosesdispensedgivesaverage
dose
4. NET CONTENTS:
 Tared cans that have beenplacedontothe fillinglineshave beenreviewedandthe difference in
weightisequal tothe netcontent
 In destructive method:weighingfillcontainerandthendispensingasmuchof the contentsas
possible.The contentsare thanweighed,thisgivesthe netcontent.
5. FOAMSTABILITY:
 Method:visual evaluationandtime for givenmasstopenetrate the foam
BIOLOGICAL TESTING:
1. THERAPEUTIC ACTIVITY:

12.  For inhalational aerosols:dosage of the productisdeterminedandisrelatedtothe particle size
distribution
 For topical aerosols:isappliedtotestareasand adsorptionof therapeuticingredientis
determined
2. TOXICITY:
 For inhalationaerosols:exposingtestanimalstovaporssprayedfromaerosol containers
 For topical aerosols:irritationandchillingeffectsare determination.