4 - Acetaminophen

Question 1

What is MOA of acetaminophen and what is it used for?

Answer 1

• Analgesic/ antipyretic that inhibits prostaglandin synthesis
• Elevates pain threshold
• Acts on hypothalamic heat-regulating center
• Used for MSK pain, earache, LBP, arthritis, dysmenorrhea, myalgia, infections

Question 2

Is acetaminophen or ASA stronger in regards to analgesic and antipyretic effects?

Answer 2

Both are considered equipotent

Question 3

Advantages of tablets over other dosage forms to manufacturers

Answer 3

• Economy
• Stability
• Convenience

Question 4

Advantages of tablets over other dosage forms to consumers

Answer 4

• Accuracy
• Portability
• Convenience

Question 5

What are some excipients found in tablets?

Answer 5

• Diluents
• Binders
• Lubricants
• Disintegrants
• Glidants
• Colorants
• Flavouring agents

Question 6

Purpose and examples of diluents

Answer 6

• Increase tablet mass for compression

- Ex: lactose, cellulose, mannitol, starch

Question 7

Purpose and examples of binders

Answer 7

• Improve free-flowing qualities of granules for desired hardness
• Ex: starch, gelatin, sugars (sucrose, glucose, dextrose), acacia

Question 8

Purpose and examples of lubricants

Answer 8

• Prevent adhesion to dies/punches, reduce friction, facilitate ejection
• Ex: talc, magnesium stearate, PEG

Question 9

Purpose and examples of disintegrants

Answer 9

• Absorb water rapidly to increase size afterwards, so tablets can disintegrate after administration
• Ex: starch, cellulose

Question 10

Purpose of glidants

Answer 10

Improve flow characteristics of a powder mixture

Question 11

Purpose of colorants

Answer 11

Provide appealing appearance

Question 12

What is used in controlled release tablets that is unique?

Answer 12

Specific polymers or coating materials

Question 13

What is the most popular tableting procedure?

Answer 13

Wet granulation

Question 14

Describe wet granulation

Answer 14

• Weighing
• Mixing
• Granulating
• Wet screening
• Drying
• Dry screening
• Lubricating
• Compressing

Question 15

Describe fluid-bed granulation

Answer 15

• Weighing

- Mixing, granulating, and drying processed in a single piece of equipment

Question 16

What is special about dry granulation?

Answer 16

• No granulation fluid so no moisture

- High temperature is applied

Question 17

What is special about direct compression?

Answer 17

• Most recent

- Mixing and compressing with shortened processing time/cost

Question 18

What characteristics describe a tablet?

Answer 18

• Tablet size, shape, thickness, weight
• Hardness
• Drug content and uniformity
• Drug disintegration and dissolution

Question 19

When is tablet hardness measured?

Answer 19

Throughout the tableting process

Question 20

Why can’t a tablet be too hard or soft?

Answer 20

• Too hard = may not meet disintegration and/or dissolution requirements
• Too soft = won’t withstand handling conditions during subsequent processing

Question 21

What determines tablet hardness?

Answer 21

Resistance to chipping, abrasion, or breakage during storage, transportation, and handling

Question 22

What is tablet friability?

Answer 22

Ability of the tablet to withstand abrasion during packaging, handling, and shipping

Question 23

When is tablet friability measured?

Answer 23

On finished products

Question 24

Which tablets normally are tested for content uniformity?

Answer 24

Those w/ small amounts of active ingredients or have small tablet weight

Question 25

What is disintegration?

Answer 25

How fast a tablet breaks into small particles once in contact w/ a medium

Question 26

Does in vitro disintegration correlate w/ in vivo?

Answer 26

Not always

Question 27

What is tablet disintegration used to measure?

Answer 27

Batch-to-batch reproducibility

Question 28

Which tablets require disintegration testing?

Answer 28

- Compressed, film-coated, enteric-coated, buccal, sublingual, soft/hard gelatin caps - Controlled release don’t require disintegration testing

Question 29

Is dissolution or disintegration more important for solid dosage forms?

Answer 29

Dissolution

Question 30

What is dissolution?

Answer 30

- Amount of time required for a given percentage of drug substance in a tablet to go into solution under specific conditions - Determines availability of an active ingredient

Question 31

What other formulations besides oral dosage forms can undergo dissolution testing?

Answer 31

Transdermal, suppositories, ointments

Question 32

What excipients were used w/ acetaminophen for this experiment and what is the purpose of each?

Answer 32

- Lactose = diluent - Avicel = binder - Explotab = disintegrant - Magnesium stearate and talc = lubricant - Granulating solution (10% PVP solution or 10% starch paste) = binder

Question 33

Which tests were performed on the tablets for this experiment?

Answer 33

- Hardness (10 tablets) using portable hardness tester - Friability (10 tablets) in a tablet friability apparatus - Weight uniformity (10 tablets) weighed them and recorded the average - Tablet content (10 tablets) - Dissolution

Question 34

How was tablet content tested?

Answer 34

- Weigh 10 tablets and find average tablet weight and grind in mortar - Weigh aliquot equivalent to 50 mg and dilute to 200 mL w/ distilled water - Filter and pipette 1 mL of filtrate into 25 mL volumetric flask and dilute w/ distilled water - Record absorbance at 249 nm w/ distilled water as blank

Question 35

How was tablet dissolution measured?

Answer 35

- Place 1 tablet in 900 mL distilled water at 50 rpm for 30 min - Withdraw 2 mL at 15 and 30 min and filter (replenish) - Pipette 1 mL of the original dissolution solution into a 25 mL flask and dilute with water - Measure absorbance at 249 nm and calculate content