Pharmaceutical drying

Question 1

Calculate the total quantity of heat required to melt 1 kg of ice if
the initial temperature of the ice is -18C.
Specific heat capacity of ice = 2.03 J g-1
K
-1
Specific heat capacity of water = 4.18 J g-1
K
-1
Heat of fusion of water = 333 J g-1
Heat of evaporation of water = 2256 J g-1

Answer 1

= Q1 + Q2
= (mcT) + mL
= (1x103 g x 2.03 J g-1
K
-1
x 18 K) + (1x103 g x 333 J g-1)
= 36,540 J + 333,000 J
= 369,540 J (369.540 kJ)

Question 2

Calculate the total amount of heat required to dry 1.5 kg of a wet
granulation at 30C with a total water content of 30 %(w/w) to a
final water content of 5 %(w/w). Assume that there are no heat
losses to the equipment or environment and all heat is transferred
to the water as sensible and latent heat.
(N.B. This is practically impossible!!)

Answer 2

Total quantity of water to be removed = 1.5 kg x 25% = 0.375 kg
Q = (mCT) + mL
= (450 g x 4.18 J g-1
K
-1
x (100-30) K) + (375 g x 2256 J g-1)
= 131,670 J + 846,000 J
= 977,670 J (977.670 kJ or 0.977670 MJ)

Question 3

3. An electric kettle is filled with 200 mL of cold water from the tap at
   a temperature of 10C. If the kettle has a rated power of 2 kW,
   calculate the time taken to boil all of the water.

Answer 3

Q = (mCT)
= 200* g x 4.18 J g-1 K-1 x (100-10) K *Assume 1 g = 1 mL
= 75,240 J
The kettle has a power rating of 2 kW  2 kJ s-1
 75,240 J / 2,000 J s-1 = 37.6

Question 4

Lactose is to be prepared in a spray-dried form for tablet
manufacture on an industrial scale. Assume that 1000 Kg of a
supersaturated solution containing 30% (w/w) lactose has been
pre-heated at the point of spray-drying and that all of the heat
transfer is in the form of latent heat.
Calculate the total quantity of heat energy that is required to
evaporate all of the water. The ‘Latent heat of evaporation’ for
water is 2256 J.g-1
.

Answer 4

Total mass of water to be removed = 1000 Kg x 70 (%w/w)
= 700 Kg
= 700 x 103 g
Q1 = mL
= 700 x 103 g x 2256 J.g-1
= 1.5792 x 109 J
(1,579.2 x 106 MJ)
(1,579,200 x 103 KJ)
(1,579,200,000 J)

Question 5

What is primary and secondary manufacturing?

Answer 5

Primary - synthesis of actives
Secondary - production of dosage form

Question 6

What is the total moisture content?

Answer 6

This is the total water content of a wet solid.

Not all of this water can be easily removed.

Easily removable water is sometimes referred to as
‘free moisture content’ or ‘unbound water’.

Question 7

What is the equilibrium moisture content?

Answer 7

All solids equilibrate with the moisture present in air.

This water is called the ‘equilibrium moisture content’.

The absolute amount is dynamic as it changes with
changes in temperature and humidity.

Each type of solid has its own ‘inherent hygroscopicity’.

Question 8

What methods are there for determining moisture content?

Answer 8

Karl-Fischer potentiometric titration
Measure the amount (moles) of water by the electrical conductivity of a REDOX titration.

Dynamic Vapour Sorption
Measure the weight change as a function of both
temperature and humidity.

Thermogravimetric analysis
Measure the weight change as a function of temperature.

Question 9

What is relative humidity?

Answer 9

Air at a given temperature will take-up water vapour.
When no more vapour can be taken-up the humidity
(ie water vapour in air) is considered to be saturated.
Like a simple ‘solution’ of water (‘solute’) in air (‘solvent’)
- increased ‘solubility’ with increased temperature,
- maximum solubility at a particular temperature,
- precipitation of the ‘solute’ on cooling.

RH %=
Vapour pressure of water vapour in air/ vapour pressure of water vapour in air saturated at the same temperature

X100

Question 10

What is RH dependant on?

Answer 10

Temperature

Question 11

What are the types of drying methods?

Answer 11

Heat sensitivity of the material to be dried,

Physical characteristics of the material,

Requirement for aseptic conditions,

Nature of the liquid to be removed,

Scale of the operation,

Available sources of heat eg electrical or steam.

Classification of drying method

Conduction Convection Radiation
(conductive) (convective)(radiative)

Question 12

What is latent heat

Answer 12

‘Latent heat’ is associated with all these phase changes

Question 13

What processes are endothermic?

Answer 13

Melting, sublimation and evaporation are ENDOTHERMIC (+Q)

Question 14

What processes are exothermic?

Answer 14

Condensation and freezing are EXOTHERMIC (-Q)

Question 15

what is evaporation?

Answer 15

Definition: To change or cause to change from a liquid state to a vapour.

Question 16

What is vapour pressure?

Answer 16

The pressure of a vapour in equilibrium with the liquid at any temperature is called the vapour pressure.

Question 17

When does boiling point occur?

Answer 17

When the vapour pressure is equal to the external
pressure, the liquid boils (ie boiling point).

Question 18

What are the three methods of heat transfer?

Answer 18

Conduction - vibration of atoms/molecules
with no appreciable movement
of molecules.

Convection - macroscopic movement of
molecules and their associated
heat energy.

Radiation - absorption of electromagnetic
rays resulting in an increase
in temperature.

Question 18

What are the three methods of heat transfer?

Answer 18

Conduction - vibration of atoms/molecules
with no appreciable movement
of molecules.

Convection - macroscopic movement of
molecules and their associated
heat energy.

Radiation - absorption of electromagnetic
rays resulting in an increase
in temperature.

Question 19

What is practical heat transfer?

Answer 19

Conduction is by far the most important
heat transfer process in industrial pharmacy
Convection in industrial processes is normally
of a forced nature rather than being natural.

Question 20

What is sensible heat?

Answer 20

Q= mc triangle T

Q = total quantity of heat (J)

m = mass of substance (kg)

c = specific heat capacity (J kg-1 K-1)

c= dQ/ mdT

dQ= chnage in heat
dT = change in temperature

1 Js-1 = 1W (Watt)

Question 21

What is latemt heat equation?

Answer 21

Heat of transformation
“…heat evolved or absorbed by a unit mass when it
changes phase without a change in temperature.”

Q=mL

Q = heat (J)

m = mass of substance (kg)

L = heat absorbed or liberated
in the change of phase of
unit mass (J Kg-1)

Question 22

How much heat is required to convert 1 g of ice at -20 C to steam at 100 C ?

Answer 22

We require to heat 1 g of ice from -20 C to 0 C
We require to melt 1 g of ice at 0 C
We require to heat 1 g of water from 0 C to 100 C
We require to evaporate (vapourise) 1 g of water to steam at 100 C

Specific heat capacity of ice = 2.03 J g-1 K-1
Specific heat capacity of water = 4.18 J g-1 K-1
Heat of fusion of water = 333 J g-1
Heat of evaporation of water = 2256 J g-1

Q1 = mcT
= 1 g x 2.03 J g-1 K-1 x (273 – 253) K
= 40.6 J

Q2 = mL
= 1 g x 333 J g-1
= 333 J

Q3 = mcT
= 1 g x 4.18 J g-1 K-1 x (373 – 273) K
= 418 J

Q4 = mL
= 1 g x 2256 J g-1
= 2256 J

QTOTAL = 40.6 J + 333 J + 418 J + 2256 J
= 3047.6 J
= 3.0476 kJ

Question 23

What is absolute zero?

Answer 23

0 K = ABSOLUTE ZERO = -273 C

Question 24

What are the advantages of Fluidised-bed drier?

Answer 24

Efficient heat and mass transfer.

Drying occurs from the surface of all individual particles.

Temperature of fluidised-bed is uniform throughout.

Some attrition of particles causes particle sphericity

Short drying times – high output/small footprint.

Question 25

What are the disadvantages of Fluidises-bed drier?

Answer 25

Excessive attrition due to turbulent state.

Production of fines (dust) – must be filtered.

Generation of static electricity – EXPLOSION RISK!!

Question 26

What is the process for spray driers?

Answer 26

Solution is atomised (aerosol) by high
pressure gradient through a nozzle.
The small spherical droplets are sprayed
into a stream of hot air.
Evaporation of the solvent (water) is
extremely fast due to the very high surface
area of the droplets.
Most of the heat is used as latent heat and
a degree of evaporative cooling takes place
- this keeps the particles from overheating
Each droplet dries to an individual solid
particle (m – mm possible).

Question 27

Spray drier simple diagram?

Answer 27

Droplet - Evaporation from surface - Conc of solute at droplet surface - hollow sphere - further drying (hole blown in sphere - shrivelled particle

Question 28

What are the advantages of spray drying?

Answer 28

Millions of small droplets give a massive
surface area heat/mass transfer and hence
very fast evaporation of solvent (water).
The characteristic (spherical) particle shape
gives the product a high bulk (tap) density
- good flowability, fast dissolution
Uniform and controllable particle size
Labour costs are low – single operation.

Question 29

What are disdvantages of spray drying?

Answer 29

Equipment is bulky (height <15 m/<dia 6 m).
Heat transfer from air is relatively inefficient

Question 30

What is spray drying used for? What are examples of materials which are spray dried?

Answer 30

Used for drying solutions and suspensions.
Reasonably useful for thermolabile materials
High outputs are possible (<2000 kg/hr) !!
Capable of producing spherical particles
suitable for dry powder inhalation products
(1-7 m)
Can be operated aseptically
Examples of materials that are spray dried
include, starches, lactose, calcium phosphate,
citric acid, powdered antibiotics etc.

Question 31

What does intergranular mean?

Answer 31

common in static bed methods such as tray driers.

Question 32

What does intragranular?

Answer 32

common in fluidised-bed and vacuum-tumbling.

Question 33

What is solute migration?

Answer 33

Solvent (water) moves towards the surface
of a solid taking undissolved solute with it.

Results from the movement of a solution
within a wet formulation.

Results in localised variation of solubilised
formulation components eg drugs.

Can be intergranular or intragranular