W23 Drying

Question 1

Purpose of drying

Answer 1

1. to improve physical form
   - improve processability (flow/ compressibility)
2. to improve stability by reducing chemical degradation
   - hydrolysis
   - conversion of polymorphic form
   - growth of micro-organisms
   - corrosion
   - efflorescence: mvm of mc inside material to outer surface
   - deliquescence

Question 2

Moisture content expression

Answer 2

mass of dry solid (kg)

Question 3

Different types of water

Answer 3

1. free water
   - easily removed, water sitting on top of material
2. bound water
   - water mc that are close and hence binds to surface of the material
3. hydrate (crystal lattice)
   - crystalline material w/ water mc within the unit cell
   - x use drying to remove water since it would convert hydrate to anhydrate
4. intracellular
   - bacteria is dried using freeze-drying

Question 4

(1) containing (2) is always surrounded by (3) that contains (4). Therefore, there is an
(5) between (6) and (7).
- RH meaning
- term related to equilibrium
- storage

Answer 4

(solid) containing (water) is always surrounded by (air) that contains (water)
therefore there is an equilibrium between (water in wet solid) and (water in the air)

• RH: relative humidity - amount of water the air can hold
• EMC: Equilibrium moisture content - point where water in solid & water in air is at its equilibrium state
  = no net change in water in solid & air
• thus, impt to find out EMC at storage conditions as drying below EMC will cause the sample to rewet with time

Question 5

Four stages of (%) drying
- each stage is limited by

Answer 5

% convective drying

1. Constant rate period
   - rate of drying ∝ heat supplied
2. First falling rate period
   - rate of evaporation - limited by rate of transfer of water from capillaries to surface
3. second falling rate period
   - rate of evaporation limited by rate of diffusion through solid
4. EMC
   - no further drying occurs as water in air & solid has reached equilibrium

Question 6

List 4 drying methods
- who
- who

Answer 6

• for solids/semi solids
  1) Tray drying
  2) Fluidised bed drying
• for solutions/suspensions
  1) spray drying
  2) freeze drying

Question 7

What are the convective drying

Answer 7

1. tray drying
2. fluidised bed drying
3. spray-drying

Question 8

Stages of convective drying

Answer 8

1. external heat transfer
2. internal heat transfer by conduction
3. internal matter transfer by diffusion
4. matter transport from product surface to surrounding air

Question 9

all drying methods are based on

Answer 9

changing position of EMC
= reducing RH of surrounding air causes solid to dry

Question 10

tray drying for what

Answer 10

small mass solid (1-2kg)

Question 11

fluidised-bed drying for what

Answer 11

large solid (>25kg)

Question 12

spray-drying for what
- main advantage (1)
- good for

Answer 12

large liquid (solutions/suspensions) in liters (L)
- can operate continuously
- good for particles for inhalation

Question 13

freeze drying for what
- good for (2)

Answer 13

small liquid (mL) - suspensions/solution

1) proteins, thermally labile drugs, bacteria
2) water-unstable drugs like penicillin
- can freeze dry drug powder and reconstitute when needed
- freeze-dried materials are porous and will dissolve easily)

Question 14

Tray drying mechanism

Answer 14

1. Material spread thinly on metal trays (= spread thinly – increases surface area)
2. Metal trays are placed in an oven
3. Stream of hot, turbulent, dry air passes over the metal trays
4. This encourages water to evaporate from solids to air

Question 15

pros and cons of tray drying

Answer 15

Advantages
1) cheap
2) easy to use
3) reliable

Disadvantages
1) can take up 24 hours to dry
2) not good for large masses of sample
3) rate of drying dependent upon air temp & by surface area of sample

Question 16

Fluidised bed drying mechanism

Answer 16

1. Underneath the hopper contains holes, which allow hot airflow to enter
2. This air flows in at high air pressure enough to lift up the (wet) powder bed
3. This causes powder to lift up & move in turbulent manner (within hot air) - Particles move in “fluidized motion”
4. This separates particles (= highly increases surface area) to allow rapid drying

Question 17

Fluidised bed drying
Lid is placed on (1) to (2)
Lid contains (3) that allows (4)

Answer 17

Lid is placed on (hopper) to prevent powder bed flying out
Lid contains filter bag with holes that allows air to flow out and to prevent explosion of container

Question 18

Fluidised bed pros and cons

Answer 18

Pros
1) rapid drying (30 mins)
2) Large SA in contact with drying air
3) uniform & precise temp control
4) can smooth particles

Cons
1) can smooth particles
- cause compaction/compression prolems
- way compacted tablet retains its strength is irregular shaped particles interlocking with each other

2) Dust, risk of explosion

Question 19

Spray drying mechanism

Answer 19

1. Both solution/suspension & hot air forced into spray-dryer through atomizing nozzle
2. This causes liquid to become atomized into small droplets & ejected into drying vertex
3. Dryer contains spinning hot air which causes droplets to spin
4. Water on droplets start to evaporate creating smaller droplets & denser particles
5. Denser the particle, more it moves to edge of chamber; hence these particles fall down at the side of the chamber & collected at bottom of chamber

Question 20

spray drying pros and cons

Answer 20

pros
1) each droplet only in contact with hot air for 1-2 seconds
- can make the material amorphous
2. Particles dry rapidly/instantaneously so reduces temperature rise & hence is economical
3. Uniform particle size
4. Produces a free-flowing powder
5. Can operate continuously (if solution inserted)

Cons
1. expensive, large size of equipment
2. large volume of air required
3. can make the sample amorphous

Question 21

Freeze drying mechanisms

Answer 21

1. Solution/suspension (to be dried) loaded into freeze-dryer at room temp, atmospheric press.
2. Material frozen (= water freezes)
3. Place material under vacuum while its frozen (= pressure reduced below 610 Pa)
4. Re-heat sample under vacuum (= causes water to sublime from solid to vapour)

Question 22

Phase diagram of water:

Answer 22

• Atmospheric pressure = 10^5
• Triple point (610Pa, 0.0075C) = point where all 3 phases exist
• Below triple point (610Pa) = material sublimes from solid to vapour

Question 23

Pros and cons of freeze drying

Answer 23

Pros
1) low temp
- good for thermally labile materials like proteins
2) makes highly porous material

Cons
1) slow, high input of energy = high cost
- so can only dry small volumes
2. material likely to be physically unstable to moisture

Question 24

Using freeze-drying as a formulation strategy

Answer 24

1. Probiotic tablet instead of suspension
   - suspension of bacteria in vial
   - freeze dry, pull the water out of bacteria (still can survive)
   - when add water again (reconstitute), bacteria recovers its viability
2. Nurofen meltet tablets
   - tablet that need water to dissolve
   - amorphous and highly porous –> desert