MANUF (LEC) -DRYING
Edrick Ramoran 3CPh
DRYING
- last stage of manufacturing before packaging
- residual moisture is low enough to prevent product
deterioration
- wet crystallized product may be freed from its residual
moisture by initial treatment in a dewatering
centrifuge
- removal of all or most of the liquid by supplying latent
heat to cause thermal vaporization
DRYING OF WET SOLIDS
MOISTURE CONTENT OF WET SOLIDS
- kilograms of moisture associated with 1kg of the
moisture-free or bone dry solid
Total moisture content
- total amount of liquid associated with a wet solid
- free moisture content- easily removable water
- equilibrium moisture content- moisture which is more
difficult to remove
- unbound water- easily removable water
- exists as a liquid and exerts its full vapour pressure
- removed readily by evaporation
- air dry- water is easily lost but the resulting solid is
not completely free from water
Equilibrium moisture content
- moisture content present in a solid under steady-state
ambient conditions
- not all possible moisture present in a wet product will be
removed because the solid equilibrates with the
moisture in air
- bound water- more difficult to remove than unbound
- adsorbed on the surfaces of solid as individual
water molecules which may form a mono- or bi-
layer on the solid surface
- absorbed water- liquid trapped in capillaries
within the solid by surface tension
RELATIVE HUMIDITY (RH) OF AIR
- increased solubility with increase in temperature
- maximum solubility at a particular temperature
(saturation)
- precipitation of the solute on cooling (condensation)
- temperature raised, take up more moisture, RH falls
- RH may rise during the process where warm air is
passed over the wet solid surface
a. Uptake of evaporated water vapour from the wet
solid
b. Cooling of the supply air as it transfers heat to the
wet solid (evaporative cooling)
- dew point- liquid water will condense and be
deposited
Wet-bulb and dry-bulb temperature
- evaporative cooling- latent heat of evaporation is
taken from the sensible heat of the water surrounding
the bulb
- keeping the bulb moist by a wet cotton wick immersed
in a water reservoir; thermometer will register a lower
temperature
Moisture content of air
- kg of water per kg of bone dry air
RELATIONSHIP BETWEEN EQUILIBRIUM MOISTURE CONTENT
AND RELATIVE HUMIDITY
- equilibrium moisture content varies with the RH
- ordinary atmospheric conditions are of the order of
20C and 70-75% RH
- mineral 1% moisture
- starch-based product 30% or more
- matl exposed to humid conditions will regain moisture
LOSS OF WATER FROM WET SOLIDS
- reduce moisture content by reducing the RH of the air
- small scale, desiccators (eg. Silica gel) --- does not take
water from solid but removes water from air
- phosphorus pentoxide has greater affinity for the water
in storage air
- moisture may be regained very quickly from the
atmosphere
TYPES OF DRYING METHOD
- convective, conductive or radiant
CONVECTIVE DRYING OF WET SOLIDS
1. Fixed (or static) bed convective drying
- Tray, shelf or compartment is the drier
Tray drier
- Directed circulation
- Air is periodically reheated after it has cooled by
passage over the wet material on one shelf before it
passes over the next
- Heat transfer from air is relatively inefficient
- Slow, can take up to 24 hours to dry
- Periodic reheating of the air is the temperature falls so
that it can pick up further moisture
- Outgoing (wetter) air contacts with the wettest
material
Rate of drying in fixed beds
- Constant-rate period- linear relationship; drying rate is
uniform
- Evaporation occurs at the surface and it remains
wet since the liquid from below replaces those
vaporized at the top
- First falling-rate period- solvent level decreases and has
to further travel to the point of evaporation
- as drying rate decreases, less heat is used as
heat of vaporization, heat input should be
reduced
- Critical moisture content- end of the constant rate
period
- Falling-rate period (second falling-rate period)- rate of
loss of moisture decreases; decrease in rate of drying
until equilibrium moisture content is reached
- Danger of overheating is highest
- Drying rate depends on the movement of the
vapour through the pores of the bed to the
surface (molecular diffusion)
 - Thermal conductivity of solid decreases as it
becomes dry
- Thermostable- safe to allow temperature
gradient to increase to maintain heat transfer
- Thermolabile- heating must be decreased
2. Dynamic convective driers
Fluidized-bed drier
- matter is contained in a vessel, the base is perforated
enabling a fluid to pass through the bed of solids
- when air velocity is low, flow takes place between the
particles without causing disturbance
- as velocity is increased, fractional drag on the particle is
equal to the force of gravity on that particle
- rearrangement of the particle occurs to offer least
resistance
- particles are suspended in air and can move
- because of great porosity, pressure drop decreases
slightly
- further increase in the air velocity causes particles to
separate and move freely- bed is fully fluidized
- any additional increase in velocity separates the
particles further, the bed expands w/o appreciable
change in the pressure drop
- velocity is sufficient to entrain the solid particles and
transport them out of the top of the bed
- boiling bed- air flowing through the bubbles
- produces conditions of great turbulence
- if hot air is used, the turbulent conditions lead to high
heat and mass transfer rates
- offers rapid drying
Advantages:
i. Short drying time
ii. Drying occurs from the surface of all individual
particles
iii. Temperature is uniform
iv. Turbulence causes attrition--- producing more
spherical free-flowing products
v. Free movement of particles--- eliminates risk of
migration
vi. Mobile containers
vii. High output due to short drying times
Disadvantages:
a) Turbulence may cause excessive attrition---
production of too much dust, damage to granules
b) Fine particles entrained in fluidizing air
c) Movement of particles my generate static
electricity (if lactose is present, ignition by static
charges and explosion can occur. Increased
danger if volatile solvent- isopropanol is present)
CONDUCTIVE DRYING OF WET SOLIDS
- Wet solid is in thermal contact with a hot surface
Vacuum oven
- Airtight seal
- 0.03-0.06 bar, water boils at 25-35C
Advantages:
a) Drying takes place at a low temperature
b) Minimum risk of oxidation since little air is present
Vacuum tumbling drier
- Heat transfer rates are higher than in convectional
vacuum oven
RADIATION DRYING OF WET SOLIDS
1. Radiant heat transmission
- no transfer medium needs to be present
Use of infrared radiation
Disadvantages:
a) absorbed very quickly and does not penetrate
far into the wet mass
b) surface layers dry quickly and the absorption of
further energy raises the temperature of the
product, which is detrimental
2. Use of microwave radiation
- wavelength range 10mm to 1m penetrates better that
IR radiation
- longer wavelength
Generation and action of microwaves
- Microwaves are produced by magnetrons
- Frequency of 960- 2450MHz to avoid interference with
radio & TV
- Molecular friction results in the generation of heat
- Loss factor is a measure of the ratio of the microwave
energy absorbed by individual molecules; the higher
the number, the greater the absorption of microwave
energy
Microwave drier for granules
- Air flow allows the continuous removal of evaporated
solvent
- Heat generated in the mass drives off the moisture and
the evolved vapour is drawn away in the air flows as it is
formed
- When drying is nearly complete, radiation field intensity
will rise
- Rise is detected and the magnetrons are turned off
automatically to give an accurate control of the final
moisture content and minimize the danger of
overheating
Advantages:
a) Rapid drying at low temperatures
b) Thermal efficiency is high
c) Bed is stationary- avoid dust and attrition
problems
d) Solute migration is reduced- uniform heating
e) Highly efficient and refined equipment
f) Granulation end-point is possible
Disadvantages:
a) Batch size is smaller
b) Can cause damage (in organs such as eyes and
testes) to operators--- put failsafe devices
DRIERS FOR DILUTE SOLUTIONS AND SUSPENSIONS
- Objective is to spread the liquid to a large surface area
for heat and mass transfer and to provide an effective
means of collecting the drying solid
- spread the liquid to a thin film on a drum
- Second, disperse the liquid to a spray of small droplets
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Drum drier
- liquid is applied to the surface of the drum and spread
to a film
- simplest method is where the drum dips into a feed pan
- rate is controlled by the speed of rotation of the drum
and temp
- drum can be heated by steam or warm water
- product is scraped by the means of a doctor knife
- for starch products, ferrous salts, suspensions of kaolin,
zinc oxide
Advantages:
a) Rapid drying
b) Equipment is compact
c) Heating time is short (few seconds)
d) Drum in a vacuum jacket (temp is reduced)
e) Product is in flake form
Disadvantages:
a) Operating conditions are critical
b) Impose careful control on feed rate, film
thickness, speed of drum rotation and drum
temperature
Spray drier
- large surface area for heat and mass transfer
- atomizing the liquid to small droplets
- drying chamber resembles a cyclone- good air
circulation, facilitates heat, encourages separation of
dried particles from air
- jet atomizers easily blocked by rapid evaporation and
deposition of solid on the nozzle and droplet size is likely
to vary
- rotary atomizer has the advantage of being equally
effective with solutions or suspensions of solid and can
operate efficiently at various feed rates
- rotates the drying droplets around the chamber to
increase residence time and drying time
- filter the air and to heat it indirectly by heat
exchanger
- uniform in appearance, easily recognizable
- particle shape is hollow sphere sometimes with a small
hole
- any substance in solution or in suspension
- most useful for thermolabile materials
- for citric acid, sodium phosphate gelatine, starch,
barium sulfate, calcium phosphate, powdered antibiotic
formulations for reconstitution to syrup, dry powder
inhalers
Advantages:
a) Millions of small droplets= large surface area for
heat and mass transfer= very rapid evaporation
(overall, few seconds)
b) Droplets do not attain high temp. Particles kept
cool by evaporative cooling
c) High bulk density= rapid dissolution (large surface
area)
d) Uniform and controllable particle size
e) Excellent flow and compaction prop for tablet
manufacture
f) Low labour costs
Disadvantages:
a) Equipment is very bulky and expensive
b) Overall thermal efficiency is low (air must be hot
when it leaves the drier to avoid condensation)
FREEZE DRYING/ LYOPHILIZATION
- dry extremely heat-sensitive materials
- allows drying w/o excessive damage of proteins, blood
products and microorganisms
- initial liquid is frozen, pressure above frozen state
reduced (pressure below triple point), water removed by
sublimation (liquid-solid-vapour; all under 0 C)
- triple point- all three phases coexist (610 Pa, 0.0075 C)
- for biological productsantibiotics, blood, vaccines,
enzyme preparations, microbiological cultures
Problems:
a) Must be within -10 to -30C
b) Sublimation only occurs at frozen surface and
slow process
c) At low pressure, large volumes of water vapour
are produced which must be rapidly removed to
prevent the pressure rising above the triple point
pressure
d) Dry material often needs to be sterile
Advantages:
a) Drying at very low temperatures- enzyme action
inhibited, chemical decomposition by hydrolysis is
minimized
b) Product is light and porous
c) Porous form is soluble
d) No concentration of the solution prior to drying
e) Oxidation is minimized
Disadvantages:
a) Porosity, ready solubility and complete dryness=
hygroscopic product
b) Very slow process, expensive
Stages of freeze drying process:
Freezing stage
- frozen before application of vacuum to avoid frothing
i) Shell freezing- fairly large volumes (blood products)
- horizontally
-slow and large crystals form= damage
blood cells and reduce viability of microbial
cultures
- vertical spin freezing
- solution supercools and freezes rapidly,
formation of small ice crystals
ii) Centrifugal evaporative freezing (ampoules) - prevents
foaming
Vacuum application stage
- drop the pressure below the triple point and remove the
large volumes of low pressure vapour formed
Sublimation stage
i) Primary drying- reduce moisture content of a freeze-
dried solid to 0.5%
ii) Heat transfer- insufficient, longer process; excess heat-
melting
- added heat but no significant increase in
temperature
- prefrozen bottles- blood, shelf- frozen materials
shelf, ampoulescentrifuge head
iii) Vapour removal- to avoid pressure rise that stops
sublimation
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 - use efficient vacuum pumps (small scaletwo-
stage rotary pumps; large scaleejector pumps)
- absorb vapour (small scaledesiccant like
phosphoruus pentoxide, cooled with solid carbon
dioxide; large scalemechanically refrigerated
condensers)
iv) Rate of drying very slow
Secondary drying
- removal or residual moisture at the end of primary
drying
- raising the temperature to 50-60 C
Influence of Process Factors on Solute Migration
Drying method
- intergranular migration- whenever temperature gradient
is present (convective drying)
- microwave radiationminimizes solute migration
- methods that keep granules in motionabolish
intergranular migration (intragranular may still occur;
fluidized bed)
- vacuum tumblingreduce migration
Initial moisture content
- greater moisture content= greater moisture movement

Packaging Practical Means of Minimizing Solute Migration

- ensure protection from moisture
SOLUTE MIGRATION DURING DRYING
- movement of a solution within a wet system
- solvent moves towards the surface of a solid
Intergranular migration- solutes move from granule to
granule
- result in gross maldistribution of the active drug
- during drying of static beds (tray drying)
Intragranular migration- solutes move towards the
periphery of each granule
a) Minimum quantity of granulating fluid and ensure
it is well distributed
b) Smallest granules that will flow easily (= large
surface area) for mottling
c) Avoid tray drying
d) Tray drying, remix before compression
e) Vacuum or microwave drying as alternative to
fluidized- bed drying --- for intragranular migration

Consequences of Solute Migration

Loss of active drug
- occurs in fluidized-bed drying
- interior has a depletion of active drug

Mottling of coloured tablets

- reduced by insoluble aluminium lake of colouring
materials
- small granules which do not fracture readily

Migration of soluble binders

- hoop stress resistance= granules harder, more resistant
to abrasion

Influence of Formulation Factors on Solute Migration

Nature of substrate
- presence of absorbent materials (starch and
microcrystalline cellulose)minimize tablet solute
migration
- granule substrate has affinity for the soluteimpede
migration
- water-insoluble lakesreduces mottling

Viscosity of granulating fluid

- impedes movement of moisture by increasing fluid
friction
- increase concentration= increase viscosity of PVP
solutionslows down migration of drugs in fixed beds
of wet granules

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