PDD 09: Solid Oral Dosage Forms – Tableting

Question 1

How are tablets formed?

Answer 1

by applying a force to a powder between two die punches

• during this process, compression and consolidation occur

Question 2

What is compression?

Answer 2

reduction powder volume by gas displacement from the powder blend

• reversible, non-destructive

Question 3

What is consolidation?

Answer 3

increasing the mechanical strength of the tablet due to interaction between particles during compression

• destructive

Question 4

What is the predominant factor for tablet strength?

Answer 4

increased particle-particle interaction due to van der Waals forces

Question 5

What are the two types of tablet presses for tablet production?

Answer 5

• single-punch press (eccentric press)
• rotary press (multistation press)

Question 6

What is a single-punch press (eccentric press)?

Answer 6

• one die and one pair of punches
• output is up to 200 tablets per minute
• force is applied from upper punch only
• primary use is in the production of small batches of tablets in R&D stage (formulation development or clinical trials)

Question 7

Single-Punch Press (Eccentric Press)

What are the stages of tableting? (3)

Answer 7

1. die filling

• powder flows into the die from the feeder by gravity
• the bottom of the die is closed off by the lower punch

2. tablet formation

• the upper punch enters the die and compresses the powder blend until the tablet is formed
• after maximum force application, the upper punch leaves the die

3. tablet ejection

• tablet is ejected from the die
• the lower punch rises to push the tablet out of the die

Question 8

Why is flowability of powders in solid drug formulations so important?

Answer 8

–

Question 9

What is a rotary press (multistation press)?

Answer 9

• primary use is for scale-up and for large-scale production
• possesses a number of dies and sets of punches
• output of over 10,000 tablets per minute
• force is applied from upper AND lower punch

Question 10

Rotary Press (Multistation Press)

What are the stages of tablet formation? (4)

Answer 10

1. compression

• upper punch enters die and gas is displaced

2. consolidation

• particle/particle interactions occur

3. decompression

• tablet ‘relaxes’ as upper punch leaves die
• tablet expands axially during this process
• if bonding between particles is not
  strong enough, the tablet will laminate

4. ejection

• tablet undergoes radial expansion
• if lamination occurs, it will occur around the upper edge of the tablet – this is called capping

Question 11

Tablet Defects

When can lamination and capping occur?

Answer 11

if particles are not compressed enough or if air is entrapped in powder bed during compression

• force transmission is not uniform throughout powder bed
• reduce compression speed

Question 12

Tablet Defects

What can lead to lamination?

Answer 12

low density zones

Question 13

Tablet Defects

What can lead to capping?

Answer 13

high density zones

Question 14

Tablet Defects

What are flowability defects?

Answer 14

• weight and dose variation
• powder sticking

Question 15

Tablet Defects

What are compactability defects?

Answer 15

• low mechanical strength
• lamination and capping

Question 16

Tablet Defects

What are friction and adhesion properties defects?

Answer 16

• excessive wear
• tablet picking – sticking of tablets to each other or tools

Question 17

When can tablet defects occur?

Answer 17

from various stages during the manufacturing process

• the whole process has to be optimized from start to finish

Question 18

Tablet Defects

What is insufficient mixing?

Answer 18

mottling: uneven distribution of colorants on surface coating

Question 19

Tablet Defects

What are chemical incompatibility and non-optimized formulations?

Answer 19

• cracking: splitting of tablet coating due to excessive expansion or poor mechanical stress resistance of coating
• peeling: insufficient adhesion between tablet core and coating

Question 20

What are the quality attributes of tablets?

Answer 20

• tablet should contain correct dose of drug
• appearance should be elegant and consistent
• drug should release from the tablet in a controlled and reproducible way
• tablet should be biocompatible
• tablet should be of sufficient mechanical strength to withstand fracture and erosion during handling
• tablet should be chemically, physically, and microbiologically stable during the lifetime of the product

Question 21

What are the tests performed to ensure tablet matches specifications?

Answer 21

• uniformity of content (amount of active ingredient(s))
• uniformity of mass
• disintegration testing
• dissolution testing
• mechanical strength testing – attrition testing (friability testing), fracture resistance testing

Question 22

Tablet Testing

What is the uniformity of content (amount of active ingredient(s)) test?

Answer 22

• collect 10 tablets and measure active ingredient(s) by an appropriate analytical method
• should be within ±15% of the average amount of active drug

Question 23

Tablet Testing

What is the uniformity of mass testing?

Answer 23

weigh 20 tablets and calculate average mass

deviation of individual masses should not exceed the following limits:

• less than 80 mg: ± 10%
• 80-250 mg: ± 7.5%
• greater than 250 mg: ± 5%

Question 24

Tablet Testing

What is disintegration testing?

Answer 24

test is carried out by agitating tablets in an aqueous medium at a defined temperature and the time to reach the endpoint of the test is recorded

• basket rack assembly with 6 open ended tubes
• mesh screen at bottom of tube
• basket raised and lowered between 29-32 cycles per minute in immersion fluid at 37°C until tablet is disintegrated

Question 25

Tablet Testing What must disintegration time be?

Answer 25

within specified range in Pharmacopoeia (usually 30 minutes)

Question 26

Tablet Testing What is dissolution testing?

Answer 26

important way to study the release of a drug from a solid dosage form in vitro - during a dissolution test, cumulative amount of drug that passes into solution is measured as function of time

Question 27

Tablet Testing Why are dissolution tests carried out to do?

Answer 27

- evaluate the potential effect of the formulation and process variables on the bioavailability of the drug - ensure that preparations comply with product specifications - indicate the performance of the preparations under in vivo conditions (must be experimentally verified)

Question 28

Tablet Testing Describe the dissolution test.

Answer 28

tablet is placed in a chamber containing dissolution medium – depends on application - ensures sink conditions - concentration gradient between diffusion layer and bulk solvent is assumed to be constant (solubility lecture) - stirred vessel methods or continuous flow methods are common

Question 29

Tablet Testing What is mechanical strength testing?

Answer 29

set of tests to determine the hardness and friability of the tablet - different sets of equipment are in use

Question 30

Tablet Testing What does the mechanical strength of a tablet affect?

Answer 30

- disintegration and dissolution rates - physical stability – breaking/chipping upon shipping and handling - ability to break tablets if needed (splitting)

Question 31

Tablet Testing What are the two most common methods of mechanical strength testing?

Answer 31

- attrition resistance tests (friability testing) - fracture resistance tests

Question 32

Tablet Testing What is attrition testing (friability testing)?

Answer 32

test meant to mimic the kind of forces to which a tablet is subjected during handling between its production and its administration

Question 33

Tablet Testing What are the methods of attrition testing (friability testing)?

Answer 33

- most common method of attrition testing involves rotation of tablets in a cylinder followed by the determination of weight loss after a given number of rotations - another method is to shake tablets intensively in a jar

Question 34

Tablet Testing What is required during an attrition test (friability test)?

Answer 34

weight loss of less than 1%, along with an absence of physical abnormalities such as capping, cracks, or fractures

Question 35

Tablet Testing What is fracture resistance testing?

Answer 35

application of a load on the tablet and determination of the force needed to fracture or break the tablet along its diameter - particularly important for blister packaged medications to ensure the tablets remain intact during their removal from the packaging