Lyophilisation technique.ppt

overview for an freeze dried technology or lyophilisation technology.

1. M. Pharm Sem-II Presentations
LYOPHILISATION
SUBMITTED TO
SAVITRIBAI PHULE, PUNE UNIVERSITY , PUNE
FOR
PARTIAL FULFILMENT OF REQUIREMENTS FOR THE AWARD OF
MASTER OF PHARMACY
IN THE SUBJECT
Pharmaceutical manufacturing technology
IN THE FACULTY OF SCIENCE AND TECHNOLOGY
BhujbalKnowledge City,
MET’s Institute of Pharmacy,
Adgaon, Nashik, 422003.
Maharashtra, India
Academic Year-2021--2021 1
Presented By-
Mr.KrishnaKhamkar
Guided By-
Dr.S.P.Ahirrao

2. Content
•Definition
•Principle
•Process
•Avdantages
•Disavantages
•Application
•Conclusion
•Reference
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3. Definition
•Astabilizingprocessinwhichasubstanceisfirstfrozenand
thenthequantityofthesolventisreduced,firstbysublimation
andthendesorptiontovaluesthatwillnolongersupport
biologicalactivityorchemicalreactions.
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4. Principle
•Freezedryingorlyophilisationistheremovaloficeorotherfrozen
solventsfromamaterialthroughtheprocessofsublimationandthe
removalofboundwatermoleculesthroughtheprocessofdesorption.
•Lyophilisationisperformedattemperatureandpressureconditionbelow
thetriplepoint,toenablesublimationofice.
•Theentireprocessisperformedatlowtemperatureandpressurebyappling
thevaccum.
•Theconcentrationgradientofwatervapourbetweenthedryingfrontand
condenseristhedrivingforceforremovalofwaterduringthe
lyopholisation.
•Sublimation of water can take place at pressures and temperature below
triple point i.e. 4.579 mm of Hg and 0.0099 degree Celsius.
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5. Cont…
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At atmospheric pressure (approx. 1,000 mbar) water can have
three physical states
Solid;
Liquid;
Gaseous.
Below the triple-point (for pure water: 6.1 mbar at 0°C), only the
solid and the gaseous states exist
Phase diagram of water

6. Steps involved in lyophilisation
Freezing
drying
•Step 1
Primary
drying
•Step 2
Secondary
drying
•Step 3
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7. Process
•Pretreatment/Formulation
•Loading/Container(ex.Flask,Vials)
•Freezingatatmosphericpressure
•PrimaryDrying(Sublimation)undervacuum
•SecondaryDrying(Desorption)undervacuum
•RemovalofDriedProductfromFreezeDryer
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8. Freeze drying(solidification)
•Freezingtheproductsolutiontoatemperaturebelowitseutectic
temperature.
•Lowtemperatureandlowatmosphericpressurearemaintained.
•Therateatwhichyoursamplefreezeswillaffectthesizeoftheicecrystals
thatform.Ifnotdoneproperly,itcanimpactthespeedofreconstitution,
lengthofthefreeze-dryingprocessandintegrityandstabilityofyour
sample.
•Unfrozenproductmayexpandoutsideofthecontainerwhenplacedunder
dryingwithhighvaccume.
•Slowercoolingresultsinlargeicecrystalsandlessrestrictionschannelsin
thematrixduringthedryingprocess.
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9. 9

10. Primary drying (sublimation)
•Sublimationiswhenasolid(ice)changesdirectlytoavaporwithoutfirst
goingthroughaliquid(water)phase.
•Sublimationisaphasechangeandheatenergymustbeaddedtothefrozen
productforittooccur.
•Sublimationinthefreezedryingprocesscanbedescribedsimplyas:
1)FREEZE-Theproductiscompletelyfrozen,usuallyinavial,flask
ortray.
2)VACUUM-Theproductisthenplacedunderadeepvacuum,wellbelow
thetriplepointofwater.
3)DRY–Heatenergyisthenaddedtotheproductcausingtheiceto
sublime.
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11. •Primarydrying(sublimation)isaslowprocessconductedatcooler
temperatures,safelybelowtheproduct’scriticalcollapsetemperature.
Sublimationrequiresheatenergytodrivethephasechangeprocessfrom
solidtogas.Allthreemethodsofheattransfer-conduction,convectionand
radiation,mustbeconsideredwhenfreezedryingaproduct.
•Whentheheatistransferredtotheflask/productprimarilythrough
convectionandradiationfromthesurroundingenvironment.Withlittle
controloverheatflowintotheproduct,itismoredifficulttocontrolthe
process.Whenworkingwithproductswithlowcollapsetemperatures,it
maybenecessarytowraporinsulatetheflasktoslowdowntherateofheat
transferandavoidcollapse.
•Inashelffreezedryer,mostoftheheatistransferredintotheproduct
throughconductionanditisimportanttomaximizethesurfacecontactof
theproduct/container/traywiththeshelf.However,theeffectsofradiation
andconvectionalsoneedtobeconsideredforproductuniformityand
processcontrolpurposes.
•convectiveheattransfercanhelppromoteuniformproductdrying.
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12. •Attheendofprimarydryingwhenallofthefreeicecrystalshavebeen
sublimed,theproductwillappeartobedried.However,themoisture
contentcanstillbeinthe5-10%rangeduetothepresenceof“sorbed”
watermoleculesattachedtotheproduct.
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13. Secondary drying (Desorption)
•Inadditiontothefreeicethatissublimedduringprimarydrying,there
remainsasubstantialamountofwatermoleculesthatareboundtothe
product.
•Thisisthewaterthatisremoved(desorbed)duringsecondarydrying.Since
allofthefreeicehasbeenremovedinprimarydrying,theproduct
temperaturecannowbeincreasedconsiderablywithoutfearofmeltingor
collapse.
•Secondarydryingactuallystartsduringtheprimaryphase,butatelevated
temperatures(typicallyinthe30◦Cto50◦Crange),desorptionproceeds
muchmorequickly.
•Secondarydryingratesaredependantontheproducttemperature.System
vacuummaybecontinuedatthesamelevelusedduringprimarydrying;
lowervacuumlevelswillnotimprovesecondarydryingtimes.
•Secondarydryingiscontinueduntiltheproducthasacceptablemoisture
contentforlongtermstorage.Dependingontheapplication,moisture
contentinfullydriedproductsistypicallybetween0.5%and3%
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14. •Inmostcases,themoredrytheproduct,thelongeritsshelflifewillbe.
However,certaincomplexbiologicalproductsmayactuallybecometoodry
foroptimumstorageresultsandthesecondarydryingprocessshouldbe
controlledaccordingly.
•Duringsecondarydrying,a“samplethief”mechanismmaybeusedto
periodicallyremovevialsfromthefreezedryerforresidualmoisture
contentdetermination.
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15. Lyophilisationsystem
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16. Freeze drying equipments
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17. Advantages of Lyophilisation
•Thermolabilematerialscanbedried.
•Prolongedshelflife.
•Freezedryingtakesplaceatverylowtemperaturesothedecompositionof
substanceisminimized.
•Stabilityoftheproductmaintained.
•Compatiblewithasepticoperations.
•Minimallossinvolatilechemicalsandheat-sensitivenutrientandfragrant
components.
•Minimalchangesinthepropertiesbecausemicrobegrowthandenzyme
effectcannotbeexertedunderlowtemperature.
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18. Disavdantages
•Volatilecompoundsmayberemovedbyhighvacuum.
•Singlemostexpensiveunitoperation.
•Stabilityproblemsassociatedwithindividualdrugs.
•Someissuesassociatedwithsterilizationandsterilityassuranceofthedryer
chamberandasepticloadingofvialsintothechamber.
•Longtimeprocess
•Manybiologicalmoleculesaredamagedbythestressassociatedwith
freeze-drying.
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19. Lyophilisedpharmaceutical products
Sr. No.LYOPHILIZED PRODUCTS PER VIAL THERAPEUTIC CATEGORY
1 ACETAZOLAMIDE INJECTION 500MG / VIAL Anti-glaucoma
2 ACYCLOVIR INJECTION
250MG/VIAL, 500MG/ VIAL,
1GM/VIAL
Antiviral
3 AMPHOTERICIN INJECTION 50MG/VIAL, 100MG/VIAL Antifungal
4
PHENYTOIN INJECTION
50MG/ML Anticonvulsant
5 AZITHROMYCIN INJECTION 500MG/VIAL Antibacterial Antibiotic
6 CASPOFUNGIN INJECTION 50MG/VIAL, 70MG/VIAL Antifungal
7 CLARITHROMYCIN INJECTION 500 MG/VIAL Antibiotic
8 COLISTIMETHATE INJECTION
100,000 IU / VIAL, 200,000
IU/VIAL
Antibiotic
9 DOBUTAMINE HCL INJECTION 50MG/ML, 250MG/VIAL Cardiac
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20. Applications
•Infoodindustry
•Inpharmaceuticalsandbiotechnology
•Otherindustries
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21. Conclusion
•Thelyophilizationtechniqueprovedtobeanadvantageforenhancingthe
stabilityoftheproductbecausethemoisturecontentoftheformulationis
greatlyreduced.
•Inthefreezedriedsolidstate,chemicalorphysicaldegradationreactions
areinhibitedorsufficientlydecelerated,resultinginanimprovedlongterm
stability
•Shelflifeoftheproductisincreasedduetolyophilisationprocess
•Thesizeoftheproductisalsoreduceandeaseforthetransportation.
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22. Reference
•The theory and practice of industrial pharmacy by Leon Lachmann, Herber
Libermanand joseph kanig.1991.pg no-62-64, 672-674
•Aultonspharmaceutics-The design and manufacture of medicines by
MichealE.Aulton,2009 pg195.
•https://www.spscientific.com/freeze-drying-lyophilization-basics/
•https://www.researchgate.net/publication/292047227_LYOPHILIZATION_
FREEZE_DRYING_-_A_REVIEW
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