Drying: - Removal of Relatively Small Amount of Water or Organic Liquids - Final Processing Step Before Packaging
Drying: - Removal of Relatively Small Amount of Water or Organic Liquids - Final Processing Step Before Packaging
Drying: - Removal of Relatively Small Amount of Water or Organic Liquids - Final Processing Step Before Packaging
2 methods of drying:
1. batch - material put into dryer & drying proceeds for a given period of time
2. continuous - material continously added to dryer & continously removed
3 catagories of drying:
• As with most operations, drying is best viewed as part of an integrated process that includes these
crystallization and isolation steps; changes in these operations can affect PSD, crystal form and
moisture content, and they can have a significant impact on the drying efficiency.
• Product drying is not a particularly energy-efficient process. Consider for example, that it can take
5-10 times the amount of energy to remove a kg of solvent in a drying operation than in a
distillation operation. Thus, it is important to remove as much solvent or moisture from the cake as
possible beforehand, and the selection of isolation equipment (pressure filter, centrifuge, etc..) has
a major impact on accomplishing this goal.
• The PSD obtained affects the efficiency of down-stream operations such as formulation and
product effectiveness such as bio-availability and shelf life.
• We will see later on in the ppt, the different types of dryers used in the Pharma industry and the
parameters to consider when selecting the equipment for a particular API process.
• It also is important to establish realistic specifications for these materials during product
development – for example, drying to “zero” moisture content is not practical – which will, of
course, depend on process requirements and material characteristics. Likewise, having robust
analytical methods for monitoring drying or for product release is critical, as is establishing safe
drying temperature ranges that will maximize drying efficiency without risking product
decomposition, melting or agglomeration
• In general terms, drying can be described by 3 processes operating simultaneously. The
first process is energy transfer from an external source to the water or organic solvent in the
material. There are two methods of transferring heat to the wet solids: direct and indirect.
When using direct dryers, Heat transfer for drying is accomplished by direct contact between
the wet solid and hot gases. The vaporized liquid is carried away by the drying medium.
Indirect dryers: Heat for drying is transferred to the wet solid through a retaining wall. The
vaporized liquid is removed independently of the heating medium. Rate of drying depends
on the effectiveness of the contact between wet material with the hot surfaces.
1. The second process is the phase transformation of the water or organic solvent from a
liquid or liquid-like state to a vapour state. Mass transfer in the solid as a liquid and a vapour
and as a vapour from the exposed surfaces. Movement within the solid results from a
concentration gradient which is dependent on the characteristics of the solid. A solid to be
dried my be porous or no porous. It can also be hygroscopic or non hygroscopic.
2. The third process is the transfer of the vapour generated away from the pharmaceutical
material and out of the drying equipment (pressure/vacuum) Analysis of the 3 processes is
complicated by the fact the 3 processes are coupled to each other, and all 3 need to be
considered simultaneously.
3. Conducting a drying study can help you determine where the major resistances to drying
occur with your product, and the best types of drying systems to deliver the characteristics
desired in pharmaceutical products.
Difference between drying and evaporation
Wet Material
Dry Material
Adiabatic dryers, solids are exposed to the
heated gasses in various methods:
• Blown across the surface cross circulation
• Blown through a bed of solids, through-
circulation; solids stationary; wood, corn etc
• Dropped slowly through a slow moving gas
stream, rotary dryer
• Blown through a bed of solids that fluidize the
particles; solids moving; frequently called
fluidized bed dryer
• Solids enter a high velocity hot gas stream
and conveyed pneumatically to a collector
Flash Dryer
Table 1 - Classification of dryers
Criterion Types
Mode of Batch
operation Continuous*
Heat input- Convection*
type Conduction
Radiation
Electromagnetic fields
Combination of heat transfer modes
Intermittent or continuous*
Adiabatic or non-adiabatic
Table 1 - Classification of dryers
Criterion Types
State of Stationary
material in Moving, agitated, dispersed
dryer
Operating Vacuum*
pressure Atmospheric
Drying Air*
medium Superheated steam
(convection) Flue gases
Drying Below boiling temperature*
temperature Above boiling temperature
Below freezing point
Table 1 - Classification of dryers
Drying temperature Below boiling temperature*
Above boiling temperature
Below freezing point
Relative motion between Co-current
drying medium and drying solids Counter-current
Mixed flow
Number of stages Single*
Multi-stage
Residence time
Short (< 1 minute)
Medium (1 – 60 minutes)
Long (> 60 minutes)
* Most common in practice
Solid drying process is very complex
with micro and nano mechanisms
Liquid movement due to capillary forces
Diffusion due to concentration gradients
Liquid vapor flow due to pressure differences
Vapor diffusion due to vapor pressure differences,
concentration differences
Osmotic pressure created by colloidal bodies has
soluble and insoluble fractions
Vapor Effusion – A relationship of vapor flow to pore
diameter
Thermodiffusion
Vaporization-condensation mechanism
The Drying Process can be classified as:
Classifications
Adiabatic Dryers are the type where the solids are dried by
direct contact with gases, usually forced air. With these
dryers, moisture is on the surface of the solid.
wet / dry
Measuring the moisture content
Many different techniques are available for measuring the moisture content of a
material. The technique used in a given instance depends upon the material being
studied, equipment available, and the time available for the measurement.
The most straightforward method of moisture measurement is to use a drying oven. A
sample of the product is heated at a specified temperature and pressure (usually
atmospheric pressure or a specified vacuum) for a specified time to remove all moisture (i.e.,
dry until there is no further weight loss). The loss in mass of the sample represents the
moisture removed from the product. The temperature, drying time, and pressure are
dependent upon the product being analyzed.
Microwave drying ovens and chemical analysis are also used for some moisture
measurement applications. An extensive list of standards for moisture measurement is
provided by AOAC (1990).
EQUILIBRIUM MOISTURE CONTENT, X*
p
• Humidity, H - kg of water vapour in 1 kg of dry air H 18.02 A
28.97 PpA
p
• Saturation humidity, HS HS 18.02 AS
28.97 Pp
AS
• Percentage relative humidity, HR HR 100 ppA ( HR HP)
AS
where
pA = partial pressure of water
vapour in air
• Humid heat, cS - amount of heat required to raise the temp. of 1 kg dry air plus
water vapour present by 1K
• Humid volume, H - total volume of 1 kg dry air plus water vapour present at 1
atm & given gas temperature
wet cloth/wick
Air flow
The Dry Bulb Temperature refers basically to the ambient air temperature. It
is called "Dry Bulb" because the air temperature is indicated by a
thermometer not affected by the moisture of the air.
The rate of evaporation from the wet bandage on the bulb, and the temperature
difference between the dry bulb and wet bulb, depends on the humidity of the air.
The evaporation from the wet muslin is reduced when air contains more water
vapor.
The Wet Bulb temperature is always between the Dry Bulb temperature and the
Dew Point. For the wet bulb, there is a dynamic equilibrium between heat gained
because the wet bulb is cooler than the surrounding air and heat lost because of
evaporation. The wet bulb temperature is the temperature of an object that can be
achieved through evaporative cooling, assuming good air flow and that the
ambient air temperature remains the same.
By combining the dry bulb and wet bulb temperature in a psychrometric
chart or Mollier diagram the state of the humid air can be determined. Lines of
constant wet bulb temperatures run diagonally from the upper left to the lower right
in the Psychrometric chart.
HUMIDITY CHART
Humidity
0.0115
HUMIDITY CHART
Humidity
is a liquid film
T2 T1
Batch Drying
If air is passed over a moist solid, air temperature will
be reduced as the water is evaporated. Calculated
through an enthalpy balance:
G
C(
Ti
To)F
wHv
To
G dFw
Hv
Water heat of
vaporization
dA T
a R
Evaporation Model; Air temperature decreases as the moisture is removed from the solid
lbs 1
R a
hr ft 2 F
Drying Curve
Drying Curve
RATE OF DRYING CURVES
• batch drying
• experimental determination
data : WS = weight of dry solid
W = total weight of wet solid vs time t
To obtain as free moisture content X vs time t:
W WS
total moisture content , Xt = WS
• batch drying
• experimental determination
dX X (0.35 - 0.325)
0.07
dt t (1.68 - 2.04)
X = (0.35 + 0.325)/2 = 0.338
R = -21.5 (-0.07) = 1.493
RATE OF DRYING CURVES
WS
t (X X )
ARC 1 2
where
RC =constant rate of drying
WS = kg of dry solid used
A = exposed surface area for drying
FALLING-RATE OF DRYING PERIOD
To determine the time required for drying from X1 to X2:
1. Graphical integration
X1
X
W 1
dX W
t
A
S
R A
S
R av
X
2
Most accurate
FALLING-RATE OF DRYING PERIOD
To determine the time required for drying from X1 to X2:
2. Special cases
WS(X1 X2 ) R1
t ln
A(R1 R2 ) R
2
FALLING-RATE OF DRYING PERIOD
To determine the time required for drying from X1 to X2:
2. Special cases
or
WSXC X C
t ln
ARC X
2
and
X
R RC
XC
EXAMPLE 9.7-1
EXAMPLE 9.7-2
Assumptions:
h(T TW )
Rate of drying, RC: RC q k yMB(HW H)
AW W
where
A = exposeddrying area (m2)
T, TW = temp. of gas & surface of solid, respectively (oC)
W = latent heat at TW (J/kg)
MA,MB = molecular weight of water & air, respectively
h = 1.17G0.37
where G = mass velocity =
To determine the time required for drying from X1 to X2:
Example 3
• A granular insoluble solid material wet with water is
being dried in the constant-rate period in a pan 0.61m
x 0.61m and the depth of material is 25.4 mm. The
sides and bottom are insulated. Air flows parallel to
the top drying surface at a velocity of 3.05 m/s and
has a dry bulb temperature of 60oC and a wet bulb
temperature of 29.4oC. The pan contains 11.34 kg of
dry solid having a free moisture content of 0.35 kg
H2O/kg dry solid, and the material is to be dried in the
constant-rate period to 0.22 kg H2O/kg dry solid.
• This will only happen if the pressure is prevented from rising above
the triple point pressure .
• 2-Sublimation can only occur at the frozen surface and is slow process (1mm
thickness of ice per hour). So, the surface area must therefore be increased and
• 3-the liquid thickness prior to freezing be reduced in order to reduce the thickness
of ice to be sublimated.
• 4-At low pressure large volumes of water vapour are produced which must be
removed to prevent the pressure rising above the triple point pressure.
• 5-The dry material often needs to be sterile, and it must also be prevented from
regaining moisture prior to the final packaging.
Stages of the freeze drying process
• 1- Freezing stage:
• The liquid material is frozen before the application of vacuum to
avoid frothing, and several methods are used to produce a large
frozen surface.
• a- Shell freezing : This is employed for large volumes such as blood
products. The bottles are rotated slowly and almost horizontally
in a refrigerated bath. The liquid freezes in a thin shell around the
inner surface of the bottle.
• Freezing is slow and large ice crystals form, which is a drawback
of this method.
• In vertical spin freezing the bottles are spun individually in a
vertical position , centrifuged and cooled by a blast of cold air. The
solution super cools and freezes rapidly, with the formation of small
ice crystals.
• b- Centrifugal evaporative freezing: The solution is spun in small
containers within a centrifuge. This prevents the foaming when a
vacuum is applied. The vacuum causes boiling at room temperature.
About 20% of the water is removed prior to freeze drying and there
is no need for refrigeration. Ampoules are usually frozen in this way
• 2 - Vacuum application stage: The containers and the frozen material
must be connected to a vacuum source sufficient to drop the pressure
below the triple point and remove the larger volumes of low – pressure
vapour formed during drying.
• 3 - Sublimation stage:
• Heat of sublimation must be supplied. Under these conditions the ice slowly
sublimes, leaving a porous solid which still contains about 0.5% moisture
after primary drying .
• Primary drying: It can reduce the moisture content of a freeze-dried solid
to around 0.5%. Further reduction can be affected by secondary drying .
• Heat transfer: Insufficient heat input prolongs the process, which is already
slow, and excess heat will cause melting.
• Vapour removal: The vapour formed must be continually removed to avoid
a pressure rise that would stop sublimation.
• Rate of drying: The rate of drying in freeze drying is very slow, the ice
being removed at a rate of about only 1mm depth per hour.
Advantages of freeze drying
• 4- Secondary drying:
• The removal of residual moisture at the end of primary drying is performed by
raising the temperature of the solid to as high as 50 or 60 C .
• 5- Packaging:
• Attention must be paid to packaging freeze-dried products to ensure protection
from moisture. Containers should be closed without contacting the atmosphere.
• Disadvantages:
• Unbound water: This water exists as a liquid and exerts its fully
vapour pressure, it can be removed readily by evaporation. During a
drying process this water is easily lost but the resulting solid is not
completely free from water molecules.
• Equilibrium moisture content:
• Bound water :
• Part of the moisture present in a wet solid may be adsorbed on
surfaces of the solid or be adsorbed within its structure to such
an extent to prevent it from developing its full vapour pressure
and from being easily removed by evaporation. Such moisture is
described as “bound” and is more difficult to remove than
unbound water.
Relative humidity (RH) of air
• Air at a given temperature is capable of taking up water vapour until
it is saturated (at 100% RH ). If the temperature is raised then the
air will be able to take up more moisture and the relative humidity
falls.
• The RH of air is dependent not only on the amount of moisture in the
air , but also on its temperature, as the amount of water required to
saturate air is itself dependent on temperature.
• 2- Efficient heat transfer per unit area (to supply sufficient latent
heat of vaporization or heat of sublimation in case of freeze-
drying)
• Tray drier:
• In Fig.26.4. tray drier. Air flows in direction of the arrows over each shelf
in turn. The wet material is spread on shallow trays resting on the shelves.
Electrical elements or steam-heated pipes are positioned as shown, so that
the air is periodically reheated after it has cooled by passage over the wet
material on one shelf before it passes on the next.
• Infrared heating has been used to dry wet granules, but it suffers
from the disadvantage that it is absorbed very quickly and does
not penetrate far into the wet mass.
• The surface layers dry quickly and the absorption of further energy
then raises the temperature of the dry material to a high value. For
this reason infrared radiation is now seldom used as a heat source
in pharmaceutical manufacture.
The use of microwave radiation
• 2- The thermal efficiency is high, as the drier casing and the air
remain cool. Most of the microwave energy is absorbed by the
liquid in the wet material.
Prefreezing
Primary Drying
Secondary Drying
Pre-freezing
Shell Freezing
Increases the surface area to volume ratio by
spreading out the frozen product inside the
vessel.
Primary Drying
Process Requires:
Prefrozen sample.
Temperature difference between sample and
collector establishes a vapor pressure
differential.(collector should be 15-20° colder than
the sample.
Heat applied to the sample.
High vacuum.
Primary Drying
Frozen
Sample
Water
Vapor
Heat Heat
Primary Drying