ERT 320
Bio-Separation
Engineering
Semester 2 2012/2013
Huzairy Hassan
School of Bioprocess Engineering
UniMAP
Product Formulation
and Finishing
Operations
“Ability to evaluate process and
important parameters involved in
purification and polishing steps
of bio-products for selected
bio-separation units”
Product Formulation and Finishing Operations
DRYING
DRYING
- Usually last step in bio-separation process, which is the
process of thermally removing volatile substances (often
water) to yield a solid.
- Reasons for drying a biological product:
It is susceptible to chemical (e.g., deamidation or
oxidation) and/or physical (e.g., aggregation and
precipitation) degradation during storage in a liquid
formulation.
 for convenience in the final use of product.
Although many bioproducts are stable when frozen, it is
more economical and convenient to store them in dry
form rather than frozen.
Drying Principle
1) Water in Biological Solids and in Gases
- Water contained within biological solids is in 2 forms:
Unbound or
free water
Bound water
- can exist in several conditions:
- is free to be in
equilibrium with water in
the vapor phase,
- Thus, has the same vapor
pressure as bulk water
- is mainly held in the voids
of the solid.
1)
2)
3)
Water in fine capillaries that exerts an
abnormally low vapor pressure because
of the highly concave curvature of the
surface
Water containing a high level of
dissolved solids
Water in physical or chemical
combination with the biological solids.
- Solids containing bound water are
called hygroscopic.
Drying Principle
- The water content of the solid is plotted as a function of the
relative humidity of air (Figure 10.1, for 3 products)
- Humidity: the mass of water per mass of dry air.
- The concentration of water, cw in moles per volume can be
related to humidity, Ἥ and total pressure, p
pw = partial pressure of water
M = molecular weight
R = ideal gas constant
Drying Principle
- The relative humidity, Rm, can be determined from pw and the
saturation vapor pressure of water pws as follows:
- A convenient way of showing the properties of mixtures of air
and water vapor mixtures is the humidity or psychrometric
chart shown in Figure 10.2.
Drying Principle
From Figure 10.2:
- Any point on this chart represents a specific mixture of air
and water.
- The curved line denoted by 100 % represents the humidity of
air saturated with water as a function of Temperature.
- Any point below 100 % or saturation curve represents air that
is unsaturated with water, and a point on the temperature
axis represents dry air.
- The wet-bulb or saturation temperature lines that slant
downward from the saturation curve are called adiabatic
cooling lines.
-As T increases, the relative
humidity decreases.
- mole fraction of water & pw are
contant as T rises, the pws rises,
thus causes Rm to decrease.
Example 10.1 Drying of Antibiotic Crystals
Air at 1 atm and 25 ⁰C with a relative humidity of 50% is to
be heated to 50 ⁰C and then to be used in drying wet
crystals of the antibiotic cefazolin sodium. The wet
crystals contain 30 g of water per 100 g of dry antibiotic.
In the drying process, the air at 50 ⁰C and the crystals
reach equilibrium with respect to the moisture.
Determine the following:
a) The percentages of bound and unbound water in the
wet crystals before drying,
b) The moisture content of the crystals after drying,
c) The water partial pressure at the drying temperature.
Drying Principle
2) Heat & Mass Transfer
Heat Transfer
- The principal heat transfer mechanisms:
 Conduction from a hot surface contacting the
material
 Convection from a gas that contacts the material
 Radiation from a hot gas or hot surface, and
 Dielectric or microwave heating in high frequency
electric fields that generate heat within the wet
material.
Drying Principle
2) Heat & Mass Transfer
Heat Transfer
Conductive
Drying
Fourier’s Law:
q = heat flux
k = thermal conductivity
y = the direction of heat
flow
Dominates in vacuum
shelf dryers, batch
vacuum rotary dryers,
and freeze dryers
-Heat is supplied through the surface of the
dryer and flows into the solids being dried.
- Either the solids on trays on heated shelves,
or moving freely inside the dryer come in
frequent contact with the surface of the
dryer.
Drying Principle
2) Heat & Mass Transfer
Heat Transfer
Convective
Drying
Q = rate of heat flow into solid
A = surface area thru which heat flows
T = gas bulk phase Temp.
= Temp. at solid surface
Predominant in
spray drying
- Involves the transfer
of heat from a moving
gas phase, providing the
heat for drying to a
solid phase
Drying Principle
2) Heat & Mass Transfer
Heat Transfer
- For both, it is more convenient to describe the system by
overall heat transfer coefficient, U:
or using volumetric heat transfer coefficient, Ua:
Drying Principle
2) Heat & Mass Transfer
-
-
Mass Transfer
Drying can be limited by mass transfer in convective drying.
The 1st water to evaporate is that next to the gas moving across the
surface of wet solids.
After an initial warming-up period, the rate of movement of water
to the surface is rapid enough that the surface remains saturated,
and the drying rate remains constant for a period of time called the
“constant drying rate period”.
During this period, mass transfer is limited by a gas boundary layer
at the surface of the solids.
At a critical moisture content Xc , however, the internal rate of
water movement is not fast enough to keep the surface saturated,
and the drying rate begins to fall.
In the falling drying rate period, the drying rate asymptotically
approaches the equilibrium moisture content Xe .
Drying Principle
2) Heat & Mass Transfer
Mass Transfer
- The mass transfer of water being evaporated at the solid surface
by gas flowing past the surface can be defined in terms of a mass
transfer coefficient, kG:
N = molar flux of water
w
Δpw= diff. in partial pressure of water
between the surface and the bulk gas stream
- During constant drying rate period, the steady-state relationship
between heat and mass transfer at the liquid surface is:
Drying Principle
2) Heat & Mass Transfer
Mass Transfer
- Eq 10.2.13 allows us to estimate the evaporation rate if we
know the heat transfer coefficient and the relevant
temperatures.
- The heat transfer coefficient has been found to vary from 10 to
100 kcal m-2h-1 ⁰C-1 for forced convection of gas.
- The temperature at the surface of a moist solid that is
undergoing drying in the constant drying rate period is usually
very nearly at the wet-bulb temperature, defined as the steady
state temperature of a small mass of water that is evaporating
into a continuous stream of humid air.
- The wet-bulb temperature is very nearly equal to the adiabatic
saturation temperature for air-water mixtures (Figure 10.2) on
the curve denoted 100 %.
Figure 10.4 Drying rate curves
for various types of materials
and mass transfer conditions.
Drying Principle
2) Heat & Mass Transfer
Mass Transfer
During the falling rate drying period, the principal mass transfer
mechanism are:
1) Liquid diffusion in continuous, homogenous materials,
2) Vapor diffusion in porous or granular materials,
3) Capillary flow in porous or granular materials,
4) Gravity flow in granular materials, and
5) Flow caused by shrinkage-induced pressure gradients.
Example 10.3 Mass Flux during the Constant Rate
Drying Period in Convective Drying.
Wet biological solids contained in a tray are dried by
blowing air with 2 % relative humidity and at 60 ⁰C
and atmosphere pressure across the tray. For the
constant drying rate period, estimate the
temperature at the surface of the solids and the
maximum molar flux of water.
Dryer Description & Operation
1) Vacuum-Shelf Dryers
Dryer Description & Operation
1) Vacuum-Shelf Dryers
-
-
Trays filled with the product to be dried rest on shelves through
which warm water or other suitable heat exchange medium is
circulated.
Heat is conducted from the shelves to the trays and into the wet
solids.
Vacuum is applied to the chamber containing trays to speed up
the drying and allow drying to take place at lower temperature.
The evaporating water vapor is drawn off in the vacuum system.
Up to several square meters of shelf area.
Used extensively for pharmaceutical products such as
antibiotics, which are often in crystalline from and exhibit
moderate to high heat sensitivity.
Dryer Description & Operation
2) Batch Vacuum Rotary Dryers
Dryer Description & Operation
2) Batch Vacuum Rotary Dryers
- Heat transfer is by conduction, also called vacuum tumble dryer.
- Heat is supplied by warm water or other heat exchange medium
circulated through a jacket on the rotating double-cone drum.
- The solids are continually tumbled by rotation of the drum, so that
solid particles comes in contact with the walls of the jacket and with
each other.
- Vacuum is applied to the rotating drum to be able to dry at lower
temperature and more rapidly.
- The volumes up to 30 to 40 m3.
- The biological products are like in vacuum-shelf dryer, but not when
the tumbling motion causes the particles to form larger and larger
balls or when the particles stick to the metal surfaces in the drum.
Dryer Description & Operation
3) Freeze Dryers
Figure 10.7
Pharmaceutical
Freeze Dryer
Dryer Description & Operation
3) Freeze Dryers
-
-
Requires both the temperature and pressure be controlled
during drying process.
The product to be dried can be either in vials or in trays.
When the vials are placed on the trays, the stoppers are
closed only partially to allow water vapor to escape.
The hydraulic piston allows for the stoppers to be
completely pushed into the top of the vials at the end of
drying.
A heat transfer fluid is circulated through the trays to
provide temperature control of the vials.
Dryer Description & Operation
3) Freeze Dryers
- Freeze drying process:
1
• Cooling of the product to a sufficiently low temperature to allow
complete solidification.
• The pressure in the chamber is then reduced to below vapor pressure at
triple point of water (0.01 ⁰C and 4.6 mmHg) so that drying can occur by
sublimation.
2
• Thus the temperature of the shelves is raised to provide energy for
sublimation.
• As drying occurs, a boundary between the dry solids and frozen
solution can be observed in each vial (Figure 10.8).
3
• Unbound water is removed in a drying phase called primary drying.
• A higher shelf temperature and additional time are required to remove
the bound water in the secondary drying phase (Figure 10.9).
• Time to complete drying cycle: 24 to 48 h.
Dryer Description & Operation
3) Freeze Dryers
Dryer Description & Operation
3) Freeze Dryers
Dryer Description & Operation
3) Freeze Dryers
- It is important that the product not exceed either eutectic
temperature or the glass transition temperature.
Otherwise the product can collapse.
The temperature in
crystalline systems
below which no liquid
exists.
Exists only in amorphous
systems and the temperature at
which there is a change in
viscosity of the system from a
viscous liquid to a glass.
Is the loss of either the
crystalline or the
amorphous structure of
product.
Dryer Description & Operation
4) Spray Dryers
Figure 10.10 Spray dryer
with a pressure nozzle
atomizer: 1-feed tank,
2-filter, 3-pump, 4atomizer, 5-air heater, 6fan, 7- air disperser, 8drying chamber, 9cyclone, 10-exhaust fan,
11-filter.
Dryer Description & Operation
4) Spray Dryers
-
-
Transform a feed in the liquid state into a dried particulate form
by spraying the liquid into a hot gas, usually air.
Utilize co-current flow of gas and feed.
3 basic unit processes involved: liquid atomization, gas-droplet
mixing, and drying from liquid droplets.
Spherical particles produced; either solid or hollow, range in
size from 2 µm to more than 500 µm.
Drying is carried out at the air wet-bulb temperature, and
drying time is measured in seconds. Inlet gas temp. can range
from 150 – 250 ⁰C.
Applied in producing milk, coffee, blood, spores and antibiotics.
Dryer Description & Operation
4) Spray Dryers
-
-
Most important operation: Atomization
Types of atomizer determines the size and size distribution of
drops and trajectory and speed.
3 types of atomizer: 1) rotary wheel (centrifugal disk),
2) pressure nozzle single-fluid
3) pneumatic two-fluid nozzles
Rotary wheel atomizer prefers for high flow rate feed streams
(>5 metric tons/h), produces relatively small particles (30 – 120
µm)
Scale-up & Design of Drying Systems
1) Vacuum-Shelf Dryers
-
The effect of changes in conditions upon scale-up can be
estimated using the time of conductive drying:
- The thermal efficiency is usually between 60 % - 80 %.
- Power can be estimated based on power to operate vacuum
system; 0.06 to 0.12 kW/m2 tray surface area for vacuums of
680 – 735 mmHg.
Scale-up & Design of Drying Systems
2) Batch Vacuum Rotary Dryers
-
-
-
In scaling-up, the heated surface area per internal volume is
not constant.
Ex: if we assume the dryer is a perfect double cone, the
heated area increases by a factor of 4.6 when the volume
increases by a factor of 10 for geometrical similarity.
Meaning  the ratio of area to volume at large scale is 46%
of the area-to-volume ratio of small scale unit with the
volume
Assuming time for drying is inversely proportional to the
area-to-volume ratio of dryer:
Scale-up & Design of Drying Systems
3) Freeze Dryers
-
Design conditions (as in Figure 10.9), determine;
1) The max allowable temperature during primary drying,
using Differential Scanning Calorimetry (DSC)
2) Chamber pressure, shelf temperature and time for
primary drying.
3) Chamber pressure and shelf temperature for secondary
drying.
Scale-up & Design of Drying Systems
4) Spray Dryers
-
Key variable: residence time of the air in drying chamber
Residence time = chamber volume / total air flow rate
Average air residence time ≈ 35 s
Assumptions:
1) Drying conditions are uniform throughout the chamber
2) Drying occurs from the drop surface
3) The h (convective heat transfer coefficient) determined by
assuming a representative drop is motionless fluid, with the
drop moving at the same speed of air.
Please study and solve this on your own
Example 10.5 Sizing of a Spray Dryer
Estimate the dimensions of a drying chamber for a
spray dryer that has an output of 1000 kg/h of a
heat-sensitive biological material at 60 ⁰C containing
5 % moisture and having a mean particle size of 100
µm. The feed contains 40% solids by weight in an
aqueous solution at 4 ⁰C. The inlet air has a humidity
of 0.01 kg/kg dry air and is at 150 ⁰C, while the outlet
air is at 80 ⁰C. Assume the specific heat of dry solids
is 0.3 kcal kg-1 ⁰C-1.
ANY QUESTIONS
THANK YOU