Pharmaceutical aerosols

Pharmaceutical Aerosols: Definition, propellants, containers, valves, types of aerosol systems; formulation and manufacture of aerosols; Evaluation of aerosols; Quality control and stability studies

2. Syllabus
Definition
Propellants
Containers
Valves
Typesofaerosolsystems
formulationandmanufactureofaerosols
Evaluationofaerosols:Qualitycontrolandstability
studies

3. Definition
Aerosolsmaybedefinedasdispersephasesystem,
inwhichveryfinesolidparticlesorliquiddroplets
getdispersedinthegaswhichactsascontinuous
phase.
Thesearealsocalledaspressurizeddosageform.

4. Advantages of Aerosols
1.Themedicamentcanbedelivereddirectlytothe
affectedareasuchasburntskinandwound.Soit
minimizesthediscomfortcausedbymechanical
ormanualapplication.
2.Absenceofairpreventsoxidationoftheproduct.
3.Thehydrolysisofmedicamentcanbeprevented.
4.Thesterilityoftheproductcanbemaintained.
5.Theapplicationofmedicamentiseasier.
6.Manualcontactwithmedicamentscanbeavoided.

5. Disadvantages of Aerosols
1.Aerosolsarecostlypreparation.
2.Someofthepropellantsareverytoxic.
3.Lotofdifficultiesarefacedinaerosolformulation
whenthedrugisnotsolubleinpropellant.
4.Thecoolingeffectofhighlyvolatilepropellants
maycausediscomfortoninjuredskin.

6. Aerosol Container

7. Aerosol container can be divided into
four parts:
1.Container
2.Valve
3.Actuator
4.Dip tubes

8. Container
❖InPharmaceuticalaerosolpackaging,the
containersaremadefrommetal(suchastinplated
steel,alluminiumandstainlesssteel)glassand
plastic.
❖Thesecontainerscanwithstandhighpressure.

9. Valves
❖Thevalvesusedshouldbesuchthatitcanbe
easilyopenedandclosed.
❖Itshouldalsodeliverthecontentinthedesired
form.
❖Threetypesofvalveusednowadays:
❑Continuoussprayvalve
❑Meteringvalve
❑Foamvalve

10. Valves….
✓Byusingcontinuoussprayvalve,themedicament
isexpelledcontinuouslyaslongaspressureis
appliedontheactuator.
✓Byusingmeteringvalve,onlydefinitequantityof
medicamentisexpelledwhenactuatorispressed.
✓Ifthecontentofaerosolarerequiredtocomeoutin
theformofaballoffoam,afoamvalveisusedin
thatcase.

11. Actuator
❖Actuatorisfittedonthevalvestem.
❖Ithelpsintheeasyopeningandclosingofthe
valve,wheneveritisrequired.

12. Dip tubes
❑Itconveystheliquidfromthebottomofthe
containertothevalveatthetop.
❑Thediptubesaremadefrompolyethyleneor
polypropylene.
❑Thediptubeshouldbeextendedalmosttothe
bottomofthecontainer.

13. Propellants
❖Thepropellantsgenerallyisregardedastheheart
oftheaerosolpackage.
❖Thepropellantisresponsiblefordevelopingthe
properpressurewithinthecontainer,anditexpels
theproductwhenthevalveisopened.

14. Propellants…..
❖Liquefied Gases
▪Chlorofluorocarbons (CFC)
▪Hydrochlorofluorocarbons(HCFC)
▪Hydrofluorocarbons(HFC)
▪Hydrocarbons (HC)
▪Hydrocarbon ethers

15. Propellants…..
❖Compressed Gases
▪Nitrogen
▪Nitrous Oxide
▪Carbon dioxide

16. Formulation of Pharmaceutical
Aerosol
Anaerosolformulationconsistsoftwoessential
components:
1.Productconcentrate
2.Propellant

17. ProductConcentrate:Theproductconcentrateconsist
ofactiveingredient,oramixtureofactiveingredients,
andothernecessaryagentssuchassolvents,
antioxidantsandsurfactants.
Propellants:Thepropellantmaybesinglepropellantor
ablendofvariouspropellants.

18. Types of systems
1.Solutionsystem
2.Waterbasedsystem
3.Suspensionsystems
4.Foamsystem

19. Manufacturing of Pharmaceutical
Aerosols
❖Toprepareandpackagepharmaceuticalaerosols
successfully,specialknowledge,skillsand
equipmentarerequired.
❑Pressurefillingapparatus
❑Coldfillingapparatus
❑Compressedgasfillingapparatus

20. Pressure Filling Apparatus
❖Pressurefillingapparatusconsistsofapressureburette
capableofmeteringsmallvolumeofliquefiedgas
underpressureintoanaerosolcontainer.
❖Thepropellantisaddedthroughtheinletvalvelocated
atthebottomortopoftheburette.
❖Trappedairisallowedtoescapethroughtheupper
valve.
❖Thedesiredamountofpropellantisallowedtoflow
throughtheaerosolvalveintothecontainerunderits
ownvaporpressure.
❖Whenthepressureisequalizedbetweentheburette
andthecontainer,thepropellantstopsflowing.

21. Cold Filling Apparatus
❖Coldfillingapparatusissomewhatsimplerthan
thepressurefillingapparatus.
❖Allthatisneededisaninsulatedboxfittedwith
coppertubingthathasbeencoiledtoincreasethe
areaexposedtocooling.
❖Itmustbefilledwithdryice/acetonepriortouse.
❖Thissystemisusedwithmeteredvalveaswellas
withunmeteredvalve.

22. Compressed Gas Filling Apparatus
❖Compressedgascanbehandledeasilyinthelaboratory
withouttheuseofelaborateequipment.
❖Sincethecompressedgasesareunderhighpressure,a
pressurereducingvalveisrequired.
❖Tousethisequipmentforfillingaerosolswithcompressed
gases,theconcentrateisplacedinthecontainer,thevalveis
crimpedinplaceandtheairisevacuatedbymeansof
vacuumpump.
❖Thefillingheadisinsertedintothevalveopening,the
valveisdepressed,andthegasisallowedtoflowintothe
container.
❖Whenthepressurewithinthecontainerisequaltothe
deliverypressure,thegasstopflowing.

23. Quality Control of Pharmaceutical
Aerosols
Propellants
▪Gas chromatography is used to determine the
identity of the propellant.
▪The purity and acceptability of the propellants is
tested by moisture, halogen and nonvolatile residue
determinations.

24. Containers..
1.Weight checking
2.Leak testing
3.Spray testing

25. 1.Weightchecking
Thisisusuallyaccomplishedbyperiodicallyaddingtothefilling
taredemptyaerosolcontainer,whichafterbeingfilledwith
concentrate,areremovedandaccuratelyweight.
2.Leaktesting
Formetalcontainers,thisisaccomplishedbymeasuringthecrimp
dimensionsandensuringthattheymeetspecifications.
3.SprayTesting
Manypharmaceuticalaerosolsare100%spraytested.

26. Valve, actuator and dip tube
❖Theyaresampledaccordingtostandardprocedures
asfoundinMilitaryStandardMil-STD-105D.
❖Toprovidethemeansfordeterminingthe
acceptanceofmetered-doseaerosolvalvesfor
pharmaceuticaluse,asuitabletestmethodwas
developedbytheAerosolSpecificationCommittee.

27. TestingProcedure
▪Twenty-fivevalvesareselectedandplacedontosuitable
containers,intowhichhasbeenplacedthespecifiedtest
solution.
▪Abutton-typeactuatorwitha0.020inchorificeattached.
▪Thecontainersareplacedinasuitableatmosphereata
temperatureof25±1⁰C.
▪Whentheproducthasattainedthistemperature,thevalve
shouldbeactuatedtothefullestextentforatleast2sec
followingcompletedispensingofasingledelivery.
▪Thetestunitisweighedtothenearestmilligram.
▪Thetestprocedureisrepeatedforatotaloftwoindividual
deliveriesfromeachofthe25testunits.

28. ValveAcceptance
Forvalvedelivering:
54µlorless,thelimitsare±15%
55to200µl,thelimitsare±10%
1.Ofthe50individualdeliveries,iffourormoreareoutsidethelimits
forthespecifiedvalvedelivery,thevalvesarerejected.
2.Ifthreeindividualdeliveriesareoutsidethelimits,another25valves
aresampled,andthetestisrepeated.Thelotisrejectedifmorethan
onedeliveryisoutsidethespecifications.
3.Iftwodeliveriesfromonevalvearebeyondthelimits,another25
valveshouldbetaken.Thelotisacceptedifnotmorethanone
deliveryisoutsidethespecifications.

29. Thank You !