Formulation of Advanced or Complex Medicines 11

Question 1

What factors lead to powder segregation (demixing)?

Answer 1

Particle size
- smaller particles have poor flow
- larger particles flow better
Particle density
- denser particles acquire greater kinetic energy
Particle shape
- spheres flow better than irregular particles
- mix better but segregate more easily
- demix

Question 2

Give three mechanisms of particle segregation

Answer 2

Vibration
Free-roll
Percolation

Question 3

What is an adhesive/interactive (ordered) mixture?

Answer 3

Mix of very small and large particles
- small particles adhere strongly to the surface of the carrier particle
- e.g. powders for inhalation
- small particles have high specific surface area

Question 4

What factors does particle size affect?

Answer 4

Rate at which substances dissolve
- surface area of powder is proportional to rate
- small particles dissolve better
Powder flow
- important for obtaining the correct dosage in each tablet/capsule
- poor flow = poor tablets/capsules
Type of powder packing
- related to shape
Powder mixing

Question 5

How can crystalline powder particle sizes be reduced?

Answer 5

Dry grinding
Dissolution (if soluble)
Suspension

Question 6

If soluble, how can particles be dried after dissolution?

Answer 6

Supercritical fluid technique
Spray drying
Precipitation

Question 7

If in a suspension, how can particle sizes be reduced further?

Answer 7

Wet grinding
- suspend particles in liquid

Question 8

Give an example where wet grinding is carried out

Answer 8

Cytotoxics to reduce dust in the air

Question 9

Why might increasing particle sizes be useful?

Answer 9

Below a certain size, powder particles will cease to flow well
- e.g. granulated vs icing sugar

Question 10

What are the advantages of granulation?

Answer 10

Improve and maintain the mixing of powders
- stops demixing

Question 11

What is granulation?

Answer 11

Process to make primary powder particles form larger multi-particulate entities called granules

Question 12

What is the size range for pharmaceutical granules?

What is the size range for particles in tablets and capsules?

Answer 12

0.2 - 4.0 mm granules

0.2 - 0.5 mm

Question 13

Why make granules?

Answer 13

To prevent segregation of components in a powder mixture to improve
- flow properties
- compaction properties
- volume of powder correct
- granulation improves compaction properties

Specific applications
- increase density of powder mix
- reduce dust when handling toxic materials
- prevent slightly hygroscopic materials caking when stored
- absorption of moisture from air

Question 14

What two processes are there of granulation?

Answer 14

Wet
Dry

Question 15

What are the advantages of wet granulation?

Answer 15

Overcomes problems with compaction of active
- many are poor
Makes particles more hydrophilic
A reliable process
- easy to transfer

Question 16

What are the disadvantages of wet granulation?

Answer 16

Requires many pieces of equipment and uses more labour
Cannot be used with water sensitive drugs

Question 17

What are particle-bonding mechanisms?

Answer 17

Mixtures of particles and liquid
- adhesion and cohesion forces in the immobile liquid films between primary particles
- interfacial forces in the mobile liquid films within granules
- solid bridges formed after solvent evaporation
Attractive force between particles
Mechanical interlocking
- powder particles that are shaped irregularly lock together

Question 18

What are the stages to the mechanisms of granule growth?

Answer 18

Coalescence
Breakage
- excipient and active into individual particles
Abrasion transfer
- excipient and active join together
Layering
- active surrounds excipient