Solid Dosage Forms: Tablets

Question 1

Define tablets

Answer 1

Compressed powders that contain API and excipients

Question 2

Discuss the application of tablets
(How are they administered?, can they treat both local and systematic conditions? Examples of oral formulations)

Answer 2

• Tablets are commonly administered orally but can also be inserted rectally or vaginally
• Can be used for both local and systematic Tx
• Some tabs are swallowed whole, chewable tablets, effeverscent tablets (dissolved or dispersed in water), sublingual/buccal tablets (retained in mouth where active substance is liberated)

Question 3

Discuss the advantages of tablets

Answer 3

1. Formulated to deliver an accurate and stable dose
2. Minute doses of drug can be administered in accurate amounts
3. Physical, chemical and microbiological stability
4. Low production costs
5. Easy to handle, package and ship
6. Enteric coating can be used to protect acid-labile drugs
7. If a fractional dose is required easy to divide into halves and quarters

Question 4

Discuss the limitations of tablets

Answer 4

1. Swallowing difficulties in unconscious, vomiting patients as well as children
2. Hydroscopic drugs (easy to absorb moisture from air - can degrade drug and excipients - if patient consumes it there will be no effect - practically tablet is useless). So not quite suitable for compressed tablets
3. Bitter taste drugs may require encapsulation prior to compression - increases production costs. Similiarly drugs that are sensitive to moisture may require coating which also increases production costs

Question 5

Define excipients

Answer 5

1. Excipients are pharmacologically inactive ingredients used as carriers for the active ingredients in a pharmaceutical product.

Question 6

What are the ideal traits of an excipient?

Answer 6

1. Pharmalogically Inert
2. Chemically and physically stable
3. Non-toxic
4. Economical
5. Non-reactive

Question 7

List the types of excipients

Fillers, binders, disintegrants, lubricants -outline function

Answer 7

• Fillers (Diluents) - provide bulk volume
• Binders - holds the powder together to form granules
• Disintegrants - Facilitates breakup of tablet
• Lubricants - reduces friction between tablet and die wall
• Glidants - increases flow-rate of granules
• Antiadherents
• Coating Agents
• ColoringAgents
• Sweeteners

Question 8

List the mechanisms of disintegration. How does the tablet break to primary particles?

Answer 8

1. Swelling
2. Cappilary action/wicking
3. Deformation
4. Particle/particle repulsive forces
5. Release of gases
6. Enzymatic action

Question 9

The powder for manufacturing tablets need to be **free-flowing. **Some materials (e.g. sugar or aspirin) are naturally free-flowing, but for most materials granulation is required to improve flowability. Poor flow propertie of the powder can alter the die filling process –> this will alter tablet weight –> variation in doses.

Please just understand this information

Question 10

What are the 3 stages in tablet manufacturing?

Answer 10

1. Die filling
2. Tablet formation
3. Tablet ejection

Question 11

Discuss the parameters that affect powder flow

Answer 11

Particle Size
1. Small particles (<50micrometres): high surface area to volume ratio - stronger interparticulate attractive forces - powder **will not flow at all **
2. Larger particles (>100 μm but < 1200 μm): tend to slide over one another -superior flow properties - VERY GOOD
3. No particle flow above 1200 up

Particle Size Distribution:
- Presence of both large and small particles enables more efficient particle packing - improves powder flow :))

Particle shape
- spherical smooth particles improve powder flow :))

Porosity and Density of Powder
- Particles with high density and low internal porosity - good flow properties of powder :))

Moisture of powder
- high moisture content - increased adhesion and cohesion – poorer flow properties of powder :((

Question 13

Outline the processes involved in direct compression

Answer 13

1. Turbular mixer is used to mix the drug + excipients
2. Tablet machine is used to compress the powder. As a result tablets are formed

Question 14

Outline the processes involved in wet granulation

Answer 14

Slide in google docs

Question 15

Outline the processes involved in dry granulation

Answer 15

Slide in google doc

Question 16

What is the “uniformity of mass” quality control test?

Answer 16

This test is done to make sure all the tablets are of uniform weight. Absolute uniformity may not be possible therefore slight variation is allowed

Question 17

List the steps to figure out the minimum tablet weight allowed and maximum tablet weight allowed.

This is step in involved in the “uniformity of content quality control test”

Slide on google docs

Answer 17

1. Find the average weight of 20 tablets exactly
   - average weight =** total of 20 tablets/20 - formula**
   E.g. average weight of 20 tablets = 50mg
2. Find out the percentage deviation allowed.
   E.g. for 50 tablets it is 10% (look at the table)
3. 10% of 50 is 5 mg
4. Subtract and add 5mg to 50 to find minimum and maximum
   E.g 50-5 = 45mg and 50+5=55mg

THUS: Minimum weight allowed = 45mg; Maximum weight allowed = 55mg
THUS; weight of tablet should be betwween 45 and 55 mg

Remember only 2 tablets should fall outside this range.

Question 18

What is the “uniformity of content (active ingredient)” quality control test?

Answer 18

Ensures that every dosage form contains equal amount of drug substance
1. Select 10 tablets at random
- PASS the test if each individual unit is between 85% and 115% of the average content.
- FAIL the test if more than one individual unit is outside these limits (85% and 115%)
OR if one is outside the limits of 75% to 125% of the average content.

Question 19

How would you evaluate the uniformity of content of an active ingredient
1. Select 10 tablets at random
- PASS the test if each individual unit is between 85% and 115% of the average content.
- FAIL the test if more than one individual unit is outside these limits (85% and 115%)
OR if one is outside the limits of 75% to 125% of the average content.

Question is on google docs

Answer 19

Sample question is on google docs

Question 20

What is the “disintegration” quality control test?

Answer 20

1. 6 tablets taken at random are placed individually in a tube
2. The tubes are vertically raised and lowered 50-60 mm, 28-32 times a minute, in a water bath at 37°C.
   - PASS if all 6 tablets have completely disintegrated within the specified time
   - FAIL if any tablet has not disintegrated.

Question 21

What is the “dissolution” quality control test?

Diagram of apparatus is in google doc notes

Answer 21

• demonstrates the appropriate release of the active substances
• 4 types of apparatus are used: the basket, the paddle, the reciprocating cylinder and the flow-through cell
• In most cases at least 75% of the active substances is released within 45 minutes

Question 22

What is the “resistance to crushing of tablets (hardness) “ test?

Answer 22

Determines the resistance to crushing of tablets, measured by the** force **needed to disrupt them by crushing

1. Select 10 tablets at random and place in a reproducible manner between the jaws of the instrument.
2. Apply pressure and measure the force at the break

Question 23

What is the friability test?

Answer 23

• To determine the physical strength of compressed tablets upon exposure to mechanical shock.

1. Weight 10 whole tablets and place the tablets in the drum
2. Rotate the drum 100 times, and remove the tablets
3. Remove any loose dust from the tablets as before, and accurately weigh.
4. A maximum loss of mass not greater than 1.0% is considered acceptable for most products