Aerosol : as drug delivery system.

This is a seminar of my M Pharm Sem-II. It consist of nearly all information about the dosage form called Aerosol in briefly. It will be helpful for the students to get insights about this topic in very simple manner.

1. 7/01/2021 1
AEROSOLS, PROPELLANTS,
CONTAINERS TYPES,
PREPARAION AND EVALUATION
Guided By :
Dr. L. R. Zawar
(HOD, Dept. of Pharmaceutics)
DEPT.OF PHARMACEUTICS/HRPIPER ,SHIRPUR
Presented By:
Gaurav ShriramPatil
M Pharm I Year (SEM II)
H.R. PATEL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH ,SHIRPUR (MH)

2. I.INTRODUCTION
II.COMPONENTS OFAEROSOLPACKAGE
III.TYPESOFSYSTEM
IV.MANUFACTURING OFPHARMACEUTICAL
AEROSOLS
V.QUALITYCONTROLOFPHARMACEUTICAL
AEROSOLSPACKAGE
VI.EVALUATIONTESTSOF PHARMACEUTICAL
AEROSOLS
VII.NEWER DEVELOPMENTS
VIII.REFERENCES
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CONTENTS

3. DEFINITION–PHARMACEUTICAL AEROSOLS
•Pharmaceuticalaerosolsaretheproductsthatarepackedunder
pressureandcontaintherapeuticallyactiveingredientthat
releaseuponactivationofappropriatevalvesystem.
•Asystemthatdependsonthepowerofacompressedtoexpel
thecontentsfromthecontainer.
•Developmentofpharmaceuticalaerosolsisoccurredin1950s.
•Theseaerosolproductswereintendedforburns,minorcutsand
bruises,infectionsandvariousdermatologicconditions.
•Aerosolproductsintendedforlocalactivityintherespiratory
tractappearedin1955,whenEpinephrinewasmadeavailable
inapressurizedpackage.
I INTRODUCTION
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4. An aerosol
product
consist of
following
component
parts:
Propellant
Container
Valveandactuator
Product
concentrate
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II COMPONENTS OF AEROSOL PACKAGE

5. Thepropellantisresponsiblefor developingthe
properpressure withinthecontainer
•Thepropellantisresponsiblefor developingthe
properpressure withinthecontainer.
•Expelstheproductwhenthevalveisopened.
•It aidsin atomizationorfoamproduction of the
product.
VARIOUS TYPES OF PROPELLANTS:
A) Liquefied Gases Propellants
B) Compressed Gases Propellants
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I PROPELLATNS

6. A)Liquefied Gases Propellants:
•These are Gases at room temp and atmospheric
pressure.
•They are liquefied by lowering the temp.
•When they are place in the container they are
immediately separated into Liquid and Vapor phase.
•They are of Following types:
CHLOROFLURO
CARBONS
FLORINATEDHYDRO
CARBONS
HYDROCARBONS
EX-di-chloro-di-
flouro-methane(12)
EX-Di-flouroethaneEX-Butane ,Propane
Used for Oral
Inhalation
preparation.
Used for Oral
Inhalation
preparation.
Used for Topical
preparation.
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7. B) Compressed Gas Propellants:
Somegasescanbecompressedinsmallvolumeand
remaininthegaseousform.Whentheseareusedto
providepressuretoremoveproductfromtheaerosolthey
cancalledascompressedgaspropellants.
•These are having High Purity
•Also, Having High Stability.
•Nitrogen, Nitrous Oxide, Carbon Dioxide are some of
its example.
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8. 7/01/2021 8
PRODUCT

9. The containers,mustwithstandpressuresas
high as140to 180psigat 130
0
F
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II CONTAINERS
Various materials
Were usedas
containers
A. Metal–
•1.Tinplatedsteel
•A.Side–seam(three
–piece)
•B.Two–piece or
drawn
•C.Tin–freesteel
•2.Aluminum
•a.Two–piece
•b.One–piece(extruded
ordrawn)
•3.Stainlesssteel
B.Glass
•a.Uncoated glass
•b.Plastic–
coatedglass

10. I.Tinplatedcontainers
•Theyconsistsofasheetofsteelplatethathas
beenelectroplatedonbothsideswithtin
•Thethicknessofthetincoatingisdescribedinterms
ofitsweight,e.g.-#25,#50and#100
•Tinplatedsteelisobtainedinthinsheets,andwhen
required,itiscoatedwithanorganicmaterial
•Thesearemostusedcontainersastheyarelight
In-expensiveanddurable.
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AMETAL

11. II.Aluminumcontainers
II. Aluminum Containers (canisters)
•Aluminumisused to manufactureextruded
(seamless) aerosolcontainers.
•Manufactured by impact extrusion process.
•Used for Inhalation and Topical aerosols.
•Light weight, Less Compatible to corrosion, less
fragile are some of advantages of Aluminum
Containers.
•Disadvantages-
a. Corroded by pure water and pure ethanol.
b. High Cost
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12. III.StainlessSteelContainers
•Thesecontainersarelimitedtothesmallersizes,
owingto productionproblemsaswellas cost.
•Theyareextremelystrong andresistanttomost
materials.
•Stainlessstealcontainershavebeenusedfor
inhalationaerosols.
•They do not require coating like other containers.
•Expensive, Restricts its size to smaller size are some
of its disadvantages.
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13. •Glasscontainersareavailablewithorwithoutplastic
coatings.
•Corrosionproblemsareeliminatedandallowsagreater
degreeoffreedomindesignofthecontainer.
•Theiruseislimitedduetobrittlenessproperty.
•UseinMDIandTopicalAerosols
•Advantages:Lesschemicalcompatibility,CorrosionFree
etc.
•Disadvantages:Accidentalbreakage,Notsuitablefor
Photosensitivematerial.
•Twotypesareavailableinthem;
1)Uncoatedglasscontainers.
2)PlasticCoatedcontainers.(preventshattering)
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B. GLASS CONTAINERS

14. 7/01/2021 14

15. Definedasadevicethatisusedtosealtheaerosol
containerandtopermitcontrolleddischargeofthe
contents.
ComponentsofValve:
Thenormalaerosolvalvehas7basicparts:
1.Actuator:Controlspattern.
2.Stem:Controlsflow
3.StemGasket:The“ON/OFF”Switch
4.Housing(Body):Enclosesspring/stem&
controlsflow.
5.SpringMounting:ClosesValve
6.MountingCup(Withmounting&gasket):The
linkbetweenthecan&valve.
7.DipTube:Drawsproductvalveupward.
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III VALVE

16. FormulationofpharmaceuticalAerosols
Containstwoessentialcomponents
Productconcentrate
Propellant
Productconcentratecontainsingredientsormixtureof
activeingredientsandothersuchassolvents,
antioxidantsandsurfactants.
Propellantmaybesingleorblendofvarious
propellants
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17. Solutionsystem(Two Phase System)
Waterbasedsystem( Three Phase System)
SuspensionorDispersionsystems
Foamsystems
1.Aqueousstablefoams
2.Nonaqueousstablefoams
3.Quick-breakingfoams
4.Thermalfoams
Intranasalaerosols
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TYPES OF SYSTEM

18. Containsbothvapor&liquidphase.
Drugsolubleinpropellant–noothersolventis
required.
Propellant12orA–70–singleormixture
Example:
Weight%
Active ingredients To 10 -15
Propellant To 100
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TWO PHASE SYSTEM

19. Largeamounts ofwater canbeusedtoreplaceallor
partof non –aqueoussolvents
Theproductsareemittedasasprayorfoam
Containswaterphase,vaporphaseandthepropellant.
Waterimmisciblewithpropellant–solubilityincreased
byadding,
Co–solvent(ethanol)
Surfactants(0.5%-2.0%)–nonpolar(esters
ofoleicacid,palmiticacid,stearicacid)
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20. Usingsuspendingagent.
Oral inhalationaerosols.
Activeingredientsdispersedinpropellantormixture
Physicalstabilityby,
-Controlofmoisturecontent
-Activeingredientswithminimumsolubilityinpropellant.
-Propellantdensity
-Suspendingagents
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21. Consistsofaq.ornonaq.vehicles,propellant&
surfactants.
Fourtypes,
Aqueousstablefoams
Nonaqueousstablefoams
Quickbreakingfoams
Thermalfoams
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22. Intendedforthedepositionofmedicationintothe nasal
passageways
Drugs intendedtoproducelocalorsystemiceffectcan
beused
Anewalternativeispressurizedmeterednasalaerosols
Advantages:
Excellentdepthofpenetration
Reduceddropletorparticlesize
Example: Oxytocin Nasal Spray.
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23. Apparatus
I..Coldfillingapparatus
II..Pressurefillingapparatus
III..Compressedgasfillingapparatus
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MANUFACTURING OF PHARMACEUTICAL AEROSOL

24. 7/01/2021 24

25. MethodA
Productconcentratechilledto-30to-40
oF.
Chilledproductaddedtochilledcontainer.
Chilledpropellantaddedthroughinletvalve.
MethodB
Productconcentrateandpropellantchilledto-30to-40
oF.
Mixtureaddedtochilledcontainer.
Thevalvesaresetinplace.
Filledcontainerspassed throughwaterbath (contentsheatedto
130
oF).
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26. Containersdried,cappedandlabeled.
Advantage
Easyprocess
Disadvantage
Aqueousproducts,emulsionscannotbefilled.
For nonaqueoussystems,moistureappearsinfinal
product.
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27. 7/01/2021 27
PRESSURE FILLING APPRATUS

28. Consistsofmeteringburette–measuresthe
amountof propellanttobe filled.
Method
Productconcentrateisfilledthroughtheburetteat
roomtemperature.
Propellantisaddedthroughtheinletvalve.
Flowofpropellantstopswhenpressureoffilling
propellantbecomeequaltothepressurewithinthe
container.
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29. Propellant–compressed gas
Pressurereducedbypressurereducingvalve
Pressureused–150psig
METHOD
Productconcentrateplacedincontainer
Valvecrimpedinitsplace
Airevacuatedbyvacuumpump
Fillingheadinsertedintovalveopening
&gasallowedtoflowintocontainer.
Containershakenduringandafterfillingby
mechanicalshakers.
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COMPRESSED GAS FILING APPRATUS

30. ItIncludesTests of:
Propellants
Valves,ActuatorandDipTubes
Containers
WeightChecking
LeakTesting
SprayTesting
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31. Vaporpressureis determinedandcompared to
Specifications
Thedensityisdeterminedby hydrometer.
PARAMETER TESTEDBY
Identification
(ofpropellantandwhen
a blend of propellant is
used , to determine its
composition)
GasChromatography
PurityandacceptabilityMoisture, Halogen,
Non-VolatileResidue
Determinations
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32. Take25valvesandplacedoncontainers
Filledwithspecifictestsolution
Actuatorwith0.020inchorificeisattached.
(containersplacedattemp.25±1
0
C)
Valveis actuatedtofullestextentfor2sec.
Repeatfortotalof2individualdeliveryfromeach
25testunits.
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33. ValvedeliveryperactuationinµL=
Individual delivery wt in mg
Specificgravityoftestsolution
ValveAcceptance
Thetestprocedureappliestotwo categoriesofmetered
aerosolvalveshavingthefollowinglimits
ForvalvesDelivering Thelimitsare
54µLorless ±15%
55to200µL ±10%
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34. Of50individualdeliveries
(1)Iffourormoreareoutsidelimits:thevalvesare
rejected
(2)Ifthreeindividualdeliveriesareoutsidelimits:
another 25 valves are sampled and the test is
repeated
Lotisrejectedifmorethanonedeliveryisoutsidethe
specification.
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35. BothuncoatedandcoatedmetalContainersare
examinedfordefectsinlining.
Qualitycontrolaspectsincludespecificationsforthe
degree of conductivity of an electric current as a
measure of exposed metal.
Glass containersexaminedfor Flaws.
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CONTAINERS
Itisdone,
»ToclearthediptubeofpurepropellantandConcentrate.
»Tocheckfor defectsinthevalveandspray pattern.
SPRAYTESTING

36. WEIGHTCHECKING
Addtaredemptyaerosolcontainertofillinglineswhichafterfillingwith
concentrateareremovedandthenweighed.
SameprocedureisusedforcheckingweightofPropellants.
Thefinishedcontainerisweighedtochecktheaccuracyoffilling.
FormetalcontainersdonebymeasuringtheCrimpdimensions&ensure
thattheymeetspecifications.
Finaltestingofthevalveclosureisdonebypassingfilled
containersthroughwaterbath.
Periodicchecksaremadeofthetemperatureofthewaterbath.
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LEAKTEST

37. A.Flammability&Combustibility
1.Flashpoint
2.FlameExtension/Projection
B.Physicochemicalcharacteristics
1. Vaporpressure
2. Density
3. Moisturecontent
4.Identification of Propellants
5.Concentrate–propellantratio
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C.Performance
1.Aerosolvalvedischargerate
2.Spraypattern
3.Dosagewithmeteredvalves
4.Netcontents
5.Foamstability
6.Particlesizedetermination
7.Leakage
D. Biological testing
1.Therapeuticactivity
2.Toxicitystudies
EVALUATION TEST OF PHARMACEUTICAL AEROSOLS

38. Flash Point Flame Projection
Theaerosolproductischilled
toatemperatureofabout-25
0F
andtransferredtothetest
apparatus
Testliquidstemperatureis
allowedtoincreaseslowlyand
thetemperatureatwhich
vapoursigniteistakenasFlash
Point.
Apparatus:OpenCupTag
This test indicateseffect of
aerosol formulation on the
extension of open flame.
Productissprayedfor4sec
intoaflame&exact lengthis
measuredwithruler.
Belowis the Apparatus used for
Flame Projection test.
A. FLAMABILITY AND COMBUSTIBILITY
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39. Property Method
1.Vaporpressure CanPuncturingDevice
2.Density Hydrometer
Pycnometer
3.Moisture KarlFischerMethod,
GasChromatography
4.Identification GasChromatography,
IRSpectroscopy
7/01/2021 39

40. 1Aerosolvalvedischargerate
Aerosolproduct ofknownweightistakenand dischargedfora given
periodof time.
By reweighing the container after time limithas expired, the changeinweight
pertimedispensedisthedischarge rate(g/sec).
2 Spray Pattern
The method is based on the impingement of spray on pieceof paperthat
hastreatedwithDye-Talc mixture
Theparticlethatstrikethepapercausethedyetogo solutionandtobe
absorbedontothepaper
Thisgivesarecordofthespraycanbeusedforcomparisonpurposes.
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41. 3. Dosage with Metered Valve
Reproducibilityofdosagedeterminedby
»AssayTechniques
Whereoneor two doses aredispensedintoasolvent orontoa
materialthatabsorbstheactiveingredients.
Thesesolutionscanthen beassayed, andtheamount of
activeingredientsdetermined.
4.Netcontents
Severalmethodscanbeused.
Taredcanshavebeenplacedontothefillinglinesare
reweighedandthedifferenceinweightisequaltothenet
content.
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42. Methods:
VisualEvaluation
RotationalViscometer
6.Particalsizedetermination
Methods:
LightScatterDecay
Cascade Impactor
7/01/2021 42
a)LightScatterDecay
Asaerosolsettlesunderturbulentconditions,thechanges
inlightintensityofaTyndallbeamismeasured

43. 1.TherapeuticActivity 2.Toxicity
•For InhalationAerosols: Depends
on theparticle sizedistribution.
•ForTopicalAerosols:Isappliedto
testareas and adsorption of
therapeutic ingredients can be
determined.
•For InhalationAerosols: Exposing
testanimals to vaporsprayedfrom
aerosolcontainer.
•ForTopicalAerosols:Irritation&
chillingeffects aredetermined.
•Degreeofchillingdependsonthe
typeandamountof propellant
present.
•Thermistorprobesattachedto
recordingthermometersusedto
indicatethechangeinskin
temperature.
7/01/2021 43

44. 7/01/2021 44
NEWER DEVELOPMENTS
•Atpresent,thereismuchinterestindevelopingMDIs
foravarietyofconditions,includingasthma,
emphysema,diabetes,AIDS,cancer,heartdisease,and
cysticfibrosis.
•Manyofthesecompoundshavebeendevelopedusing
biotechnologyprocesses,andtheirdeliverytothe
respiratorysystemviaanMDIisanextremely
challengingundertaking.
•Withtheintroductionofnewer,alternativepropellants,
thechallengebecomesevengreaterandpresentsa
uniqueopportunityforthedeliveryofthesecompounds.

45. Lachman,L.,Lieberman,HA.,2009.Thetheoryandpracticeof
industrial pharmacy, special Indian ed. CBS publishers and
distributorsPVT.LTD,NewDelhi, 589-618.
Sciarra, JJ., Stoller, L., 1998. The science and technology of
aerosolpackaging.AWiley–intersciencepublication,Newyork,
247-255.
John J Sciarraand ChristhopherJ Sciarra, Remington Essentials
of Pharmaceutics, Edited by Linda Felton, 633-651.
Search Engine: Google and You tube.
Wikipedia.
7/01/2021 45
REFERENCES