freeze drying-1.pdf

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1. Freeze drying
SANA INAM
Assistant Professor
Faculty of pharmaceutical sciences

2. Freeze dryer (FD)
Also called :
Gelsication/ Lyophillization/ Drying by sublimation /cold drying
Early applications ------drying of blood plasma and serum during World War II.
Principle:
In freeze drying water is removed from the frozen state by sublimation(direct change of
water from solid into vapour)

3. Principle

4. Phase diagram of water
Thediagramconsistsofthreeseparateareas
representingthephasesofwater,solid,liquid,
andvapour.ThepointAistheonlypoint
whereallthethreephasescancoexist,andis
knownasthetriplepoint.
Onheatingatconstantatmosphericpressure
icewillmeltwhenthetemperaturerisesto
zerodegC.
Atthisconstanttemperatureandpressureit
willchangeintowater.
Comtinuedheatingto100degCwillraise
temp.soliquidwaterwillconvertintovapour
water
If,solidice,ismaintainedatapressure
belowthetriplepoint,thenonheating,itwill
sublimeanddirectlypasstowatervapour
withoutpassingthroughtheliquidphase.

5. Phase diagram of water
Thus sublimation will occur at a temperature (0.0099 ) and pressure (4.58 mm Hg
/0.00603atm), below the triple point of water (alone)
The water in pharmaceutical solids intended for freeze drying contains dissolved solids----
resulting in different temp. pressure relationship for each solute
In such cases, the temp. & pressure at which frozen solid vaporizes without converting into
liquid is called eutectic point.
freeze drying is carried out at temp. & pressures well below this point
In actual, freeze drying of pharmaceuticals is carried out at temperatures as low as -40 degC
(e.g., for glucose and fructose) or -10 degC(e.g. for starches an d proteins)& at pressure of
2000 to 100 m Torrs( 2.6-0.13 m bar).

6. Basic requirements for freeze drying
Three
1.The vapour preesure of water on the surface of material to be dried must be higher than
the partial pressure of surrounding atmosphere
2.Latent heat of vaporization must be introduced to drying solid at such a rate so as to
maintain the desireable temperature levels at both the surface and interior
3.Provision must be made for removal of evaporated moisture

7. Freeze dryer
Construction:
Freeze dryer consists of
1.Drying chamber in which trays are loaded
2.Heat source (heat is supplied by conduction, radiation or both)
3.vaccum source (Vacuum pump or steam ejectors or both )
4.vapor removal system( 3 methods employed, condensor, dessicants and pumps)

8. Freeze dryer
https://youtu.be/9iS0usklM58

9. Freeze dryer
Working:
It involves following steps
1.Preparation and pretreatment
2.freezing for solidifying water
3.Primary drying (sublimation of ice)
4.Secondary drying (removal of residual moisture)
5.Packing

10. Freeze dryer
1-Preparation and pretreatment:
solution is pre concentrated under normal vacuum tray drying (reduces the actual drying by 8
to 10 times)
Formulation revision ( add cryoprotectant e.g DMSO,glycerol, polyethylene glycol etc. to
increase stability and/or improve processing)
Increase surface area
final product becomes more porous.

11. Freeze dryer
2-freezing for solidifying water
Vials, ampoules or bottles in which the aqueous solution is packed are frozen in cold shelves
about -50 deg C to -80 deg C
1.Shell freezing and Vertical spin freezing ( vials & bottles)
done by mechanical refrigeration by using dry ice or liquid nitrogen
2.cetrifugal evaporative freezing (ampoules)
without rerfrigeration & under low pressure by using pumps ( rotary /ejector pumps)
12

12. Freeze dryer
3-Primary drying (sublimation of ice)
material to be dried is spread as much large surface as possible for sublimation.
Temperature and pressure should be below the triple point of water
The rate of sublimation of ice from a frozen product depends upon the difference in vapor
pressure of the product compared to the vapor pressure of the ice collector
heat is transfer as latent heat and ice sublimes directly into vapour state.
vapour molecules formed must be removed continually to avoid a pressure rise that would
stop sublimation
Dessicant on small scale , conndensor or pumps ---large scale
95-98% water is removed (20 -24 Hrs.)

13. Freeze dryer
4-secondary drying
After primary freeze-drying is complete, and all ice has sublimed, bound moisture is still present in the
product.
product appears dry, but the residual moisture content may be as high as 7-8%
continued drying is necessary at warmer temperature (50 to 60ºC) to reduce the residual moisture
content to optimum values. ( 8-10 Hr.)
This process is called ‘Isothermal Desorption’ as the bound water is desorbed from the product.
5-Packing
Vaccum replaced by filtered air or inert gas N2
Ampoule sealed by tip sealing
Vials & bottles by rubber closure and Al caps

14. Advantages
1.Freeze drying is a process used to dry extremely heat –sensitive materials.
2.It allows drying , without excessive damage, of proteins, blood products ,
antibiotics,steroids and enzymes
3.Material can be dried in final container (single dose or multiple dose vials)
4.No need to use chemicals for preservation
5.Easy to transport
6.Can reconstitute quickly and easily
7.Can increase the shelf life
8.No risk of contamination

15. Disadvantages
1.Expensive (high cost of freeze drying discourages its wider application)
2.Long process time
3.Effective for selected items
4.Difficult for solutions containing nonaqueous solvents
5.The product is prone to oxidation due to large surface area & high porosity so the product
should be packed under vaccum or using inert gas or in vials impervious to gases

16. Marketed products