AMH EXAM SAQ

Explain the difference between primary and secondary nucleation in a crystallisation process.

• Primary: the initial formation of a crystal where none are currently present or if present have no effect on the process

• Secondary: Process by which new crystals form from existing crystals. It occurs at lower levels of supersaturations than primary nucleation

What is cake filtration? Outline why filter aids may be required in some cake filtration processes

Cake filtration is when a liquid with a solid material is filtered, solid accumulate and form a cake on top of the filter medium. It acts as a true filter 

Filter aid is added when the material you want to filter out doesn’t form a good filter cake. When added to liquid to be filtered it reduces resistance of filter cake and increases filtration

In the context of particle size analysis define/explain each of the following, including appropriate labelled diagrams, as necessary, to support your answer: 

(i) The difference between the median particle size and a mean particle size

i) 

Median particle size: particle diameter at which 50% of the particles are smaller and 50% are larger

Read at 50% on the cumulative distribution curve

Median is not affected by extreme particle sizes 

Mean particle size is an average value calculated by weighting particle diameters according to a chosen property 

The mean depends on the method used and the type of distribution

In the context of particle size analysis define/explain each of the following, including appropriate labelled diagrams, as necessary, to support your answer: 

(ii) The difference between a frequency particle size distribution and a cumulative particle size distribution 

ii)

Frequency particle size distribution

• Shows the amount of particles within each size range 

• Y axis represents number, weight, or volume fraction 

• X axis represents the particle size

• Mode - appears as the peak on the curve 

Cumulative particle size distribution

• Shows the total percentage of particles below or above a given particle size 

• Always increases from 0% to 100%

• Used to determine the median and other percentiles - D10, D90

In industrial crystallization, what is meant by “seeding” and why is it used? 

Seeding means adding small preformed crystals of the desired substance to a supersaturated solution 

It is used to control nucleation and crystal growth giving better control over crystal size, shape and purity and to prevent unwanted spontaneous nucleation

What is a filter aid and why are filter aids sometimes required in cake filtration processes? 

Materials which are added in concentrations of up to 5% to slurries which filter only with difficulty 

Filter aids are used to improve filtration rate by preventing clogging of the filter medium, increasing cake porosity and reducing resistance to liquid flow

Advantages and disadvantages of laser diffraction for particle size analysis compared to other sizing methods
ADVANTAGES:

• Fast analysis 

• Wide particle size range

• Non intrusive technique

• High precision and producibility 

• Considered an absolute measurement 

• Simple to use

Advantages and disadvantages of laser diffraction for particle size analysis compared to other sizing methods

DISADVANTAGES:

• Measures a volume distribution only 

• Assumes particles are spherical

• Requires refractive index difference 

• Expensive equipment

• No particle shape info

5 characteristics of an ideal solvent for cooling crystallization

-          Dissolve all the compound when the solvent is hot

-          Dissolve minimum amount of compound when the solvent is at room temp

-          Different solubility to the compound and impurities

-          Lower BP and MP of compound

-          Cheap, non toxic, non reactive

-          Low BP

Describe the main types of stresses involved in pharmaceutical milling and explain how they contribute to particle size reduction.

• Compressive stress: particle size reduction by applying force slowly to the particle in a direction toward the centre of the particle 

• Impact stress: particle size reduction by applying an instantaneous force perpendicular to the particle surface 

• Tensile stress: apply stress away from centre of particle - trying to pull it apart 

• Shear stress: particle size reduction by applying force in a direction parallel to the particle surface 

• Attrition - shear force arises from particle particle contact

Briefly explain how crystallization arises in a cooling crystallization process.

- Supersaturated solution occurs at high temp

- Solution is cooled at lower temp – this decreases the solute solubility in solution

- Crystals form