Powders for Pharmaceutical use: API and excipients Part 2

Question 1

Why is flow important in powders?

Answer 1

1. Helps the industrial manufacturing process be more efficient
2. Can fill the tablet die and capsule more easily
3. If not, can get different tablet weights

Question 2

What are the two problems that can occur if the flow isn’t correct?

Answer 2

1. Poor flow can introduce air into the mix which can lead to:
2. Capping
3. Lamination

Question 3

Describe what capping is?

Answer 3

When the cap of a tablet breaks off due to poor flow

Question 4

Describe what lamination is?

Answer 4

Break up of the tablet into many layers that usually occurs in the middle of the tablet due to gaps of air from poor flow

Question 5

Describe the surface effects of adhesion and cohesion, and what are the forces involved for each of them?

Answer 5

1. Adhesion: the sticking of solid particles between two unlike particles
2. Cohesion: the sticking of solid particles between two alike particles
3. Van der waals and electrostatic

Question 6

How do spheres influence the particle shape?

Answer 6

1. Have minimum inter-particle contact compared to flakes

2. Lower surface area per volume

Question 7

How does being more dense influence the particle density?

Answer 7

1. Less cohesive (flow by gravity)

2. Due to them weighing more

Question 8

Describe what main flow is?

Answer 8

1. Free flowing, first particle in is the first one out

2. Whole powder bed moves down

Question 9

Describe what Funnel Flow is?

Answer 9

1. Cohesion on the side of the walls
2. Powder flows right down the middle
3. Causes erratic flow and poor filling

Question 10

Describe what segregation is and used for?

Answer 10

1. Process by where different particle sizes in a powder separate
2. Generally poured into a heap that results in a segregation from a hopper

Question 11

What are the four ways to improve flow?

Answer 11

1. Change particle size and size distribution:
   - use sieves
   - make granules flow better
2. Reduce inter particle forces
   - Pour slowly
   - Avoid moisture as it can cause cohesion
3. Add excipients
   - Glidants such as magnesium sterate, talc, silicon dioxide
4. Change manufacturing equipment
   - Vibrating hopper

Question 12

Describe the role of compressibility?

Answer 12

1. Compresses to form a tablet from excipients and API
2. Most APIs tend to be relatively potent and require low doses
3. Nature of API has influence over quality of tablet

Question 13

What are plastic materials in relation to tableting?

Answer 13

1. Deform by changing shape to bind together
2. On compression do not get new surfaces forming
3. Can add brittle excipient: lactose

Question 14

What are elastic materials in relation to tableting?

Answer 14

1. Recovers their shape after tableting
2. If bonding is weak, capping will occur
3. Example: Paracetamol

Question 15

What are brittle materials in relation to tableting?

Answer 15

1. Fragment on compression (not bind together)
2. Exposes new surface
3. Lead to high friability
4. Add excipient such as microcrystalline cellulose that has plastic properties

Question 16

Why is measuring sticking important in compressibility?

Answer 16

1. If powder is sticky, it will adhere to the punch and die

2. Can lead to variable target weights

Question 17

What are organoleptic properties?

Answer 17

1. In relation to tablets, relates to the sense of smell, touch, taste and visually
2. Considers: dryness, moisture, and stale fresh factors

Question 18

How do you improve the organoleptic property of taste?

Answer 18

1. Use water insoluble derivatives
2. Add flavours:
   - Citrus- mask sour
   - Sweet- mask bitter
   - Fruity flavour- mainly for children

Question 19

How do you improve the organoleptic property of smell?

Answer 19

Use perfumes for topical products

Question 20

How do you improve the organoleptic property of colour?

Answer 20

1. Mask colour changes
2. Aid tablet recognition
3. Should match taste and smell

Question 21

What are the therapeutic consideration that should be taken when forming an oral form?

Answer 21

1. Length of therapy:
   - Reduce frequency of dosing
2. Speed of onset:
   - Fast: quick dissolution
   - Long duration: sustained release
3. Age of patient:
   - Children choke on tablets- use solution
   - Elderly don’t want to measure solution- use tablets

Question 22

What is the purpose of the formulation stages?

Answer 22

1. The physicochemical properties of the API have been chosen and are suitable
2. Must move towards manufacturing, dosage form and making it into a medicine
3. This includes: quality control checks and excipients

Question 23

Describe the initial formulation development and the purpose of it?

Answer 23

1. Uses small scale equipment such as those in labs to formulate small batches
2. Want to find out if the formulation is suitable for manufacture
3. If there is a way to improve its properties: using granules to improve flow
4. Can the dosage form be developed and scaled up on a large scale

Question 24

What does the preliminary dosage form of formulation assess?

Answer 24

1. The physicochemical properties of the API
2. Chemical purity
3. Testing it against animals to see the pharmacokinetic properties to API alone
4. Stability when put under storage or specific packaging
5. Batch to batch variation
6. Marketing: can we sell the dosage form?

Question 25

What does the process development formulation assess?

Answer 25

1. Scaling it up to large scale
   - Batch will take longer as you have to clean the equipment
2. Takes the formulation that has been developed and defines manufacturing step
3. Checks:
   - Storage
   - Batch to batch
   - Packaging
   - Stability
   - Equipment required
   - Regulatory requirements