Tablets I

Question 1

What are tablets?

Answer 1

Tablets are a unit dose form of medication containing one or more drugs to which excipients may have been added and compressed as granules or powder to a definite shape
They are a very popular dose form and 70-80% of all medications taken are in tablet form
Popularity is due to a number of factor

Question 2

What factors make tablets popular?

Answer 2

Dosing accuracy
Stability
Patient acceptance
Diversity

Question 3

Why is dosing accuracy an advantage for tablets?

Answer 3

Each tablet contains a precise dose and content is uniform within specified limits

Question 4

Why is stability an advantage for tablets?

Answer 4

Drugs in solid state generally are more chemically stable

May be coated to protect from the environment and stomach acid and stabilizing agents may be added for formulation

Question 5

Why are tablets accepted by patients?

Answer 5

Small bulk and conveniently carried by patient
Objectionable odor/taste can be masked by a variety of techniques
Attractive appearance

Question 6

Why is diversity an advantage for tablets?

Answer 6

Most tablets are intended to be swallowed but there is also sublingual, implant, chewable
Drug release may be immediate, sustained, repeat or may be designed to release drug at a specific site along the GI tract

Question 7

What are some disadvantages to tablets?

Answer 7

Solid dose form may cause local irritation to the GI mucosa

May have bioavailability problems since dissolution must occur before drug is available for absorption

Question 8

Tablets must have a number to attributes. What are they?

Answer 8

Able to withstand the rigours of mechanical treatment during production, packaging, shipping and dispensing
Free of defects (cracks, chips, discolouration)
Reasonable chemical and physical stability
Contain the proper amount of medication and release it in a predictable and reproducible manner

Question 9

Materials intended for compression into a tablet must have two essential characteristics. What are they?

Answer 9

Fluidity is necessary for the transport of the material through a hopper into a feeder frame or die cavity
Compressibility is the property of forming a stable compact when pressure is applied

Question 10

Why are granules better than powders for producing tablets?

Answer 10

Powders generally do not flow freely and the hopper may become plugged by bridging or may form a rat hole
Poor flow will lead to variable fill of the cavity and consequent variation in tablet weight, content and hardness
Granules are free-flowing and have good compression properties

Question 11

Good granulation should have what attributes?

Answer 11

Should approach spherical shape (minimize inter-particle friction and static charge)
Should present a narrow range of particle size (provide uniform fill and bridges between particles when compressed)
Should have homogeneous distribution of all materials (tablets must have content uniformity)
Should have acceptable compression properties (tablet hard enough to remain intact yet be able to disintegrate when taken)

Question 12

What should be considered when formulating granules?

Answer 12

To produce granules, additives or excipients generally must be used to confer appropriate properties to the granules. Some aid in granule formation and flow, some aid in compression and some aid in disintegration and dissolution
Excipients must not comprise product stability and must conform to pharmacopeial standards
With wide range of excipients, a tablet is a fairly complex dose form

Question 13

Why are diluents important?

Answer 13

Potent drugs may have a dose in the microgram range and a diluent or filler must be used to give the product adequate bulk

Question 14

What are examples of diluents?

Answer 14

Lactose, sucrose, mannitol, sorbitol, calcium sulfate, calcium phosphates, starch, microcrystalline cellulose
Choice of filler is determined by desired specifications and stability/compatibility aspects of API

Question 15

Describe lactose as a diluent

Answer 15

Common diluent
Inexpensive, readily soluble and reasonably inert
Crystals tend to be plastic and deform under pressure so good compressibility properties
Not hydroscopic
Prone to “browning” with some drugs and may lose compression characteristics with some drugs

Question 16

Describe sucrose as a diluent

Answer 16

Often used to impart hardness to tablets but used in small amounts since it is somewhat hydroscopic
Tablets containing sucrose tend to harden with time
Subject to browning with some drugs

Question 17

Describe mannitol as a diluent

Answer 17

Inert and non-hydroscopic

Used in chewable tablets because of mouth-feel properties (cool, smooth, slightly sweet)

Question 18

Describe calcium sulfate as a diluent

Answer 18

Low solubility and non-hydroscopic
Inexpensive and useful for acidic, neutral and basic drugs
Good absorption of oils
Inert but combined with sugars, tends to harden with time

Question 19

Describe microcrystalline cellulose (MCC)

Answer 19

Insoluble, inert free-flowing filler which can also function as binder as disintegrate
Widely used in direct compression
May be added dry to granules to improve binding but is relatively expensive

Question 20

What are binders?

Answer 20

They hold powders together by adding cohesive forces to the diluent and are used as needed
Used with care since tablet must disintegrate at some point
Usually sugars or polymers and are added as solutions or slurries to powdered material

Question 21

What are examples of binders?

Answer 21

Starch (5-10% aqueous paste)
Pregelatinzed starch (5-10% added dry)
Gelatin (2-10% aqueous solution)
Polyvinylpyrrolidone (5-20% aqueous or alcoholic)
Methylcellulose (2-10% aqueous solution)
Ethylcellulose (5-10% alcoholic solution)
Polyvinyl alcohols (5-20% aqueous solution)

Question 22

Describe starch (corn) as a binder

Answer 22

Most common binder
Neutral and non-reactive
Also functions as a disintegrating agent
May give soft granules so additional excipients may be required

Question 23

Describe gelatin as a binder

Answer 23

Stronger bind than starch

Use largely replaced by synthetic polymers

Question 24

Describe natural gums as binders

Answer 24

Acacia and tragacanth while still used, largely replaced by synthetic polymers
Bacterial contaminants are a problem

Question 25

Describe polyvinylpyrrolidone (PVP) as a binder

Answer 25

Popular and very useful binder
Slightly hydroscopic
Able to use alcoholic or hydro-alcoholic solvents

Question 26

Describe cellulose derivatives as binders

Answer 26

Good binding properties and very versatile
Some are alcohol soluble
Most common are methyl cellulose carboxymethylcellulose (CMC), ethyl cellulose and hydroxypropylmethylcellulose (HPMC)

Question 27

What are lubricants used for?

Answer 27

Used to ease the ejection of the tablet from the die to prevent sticking to the faces of the punches and to reduce wear on the tooling
Applied to coat granules therefore particle size of lubricant is important since we want uniform coating
They may be water soluble or water insoluble depending on product requirement
Magnesium stearate is widely used
Slightly alkaline which may cause problems and tend to waterproof granules which may affect disintegration/dissolution properties of tablets

Question 28

What are examples of lubricants?

Answer 28

Magnesium stearate
Calcium stearate
Zinc stearate
Sodium benzoate
Light mineral oil
Polyoxyethylene monostearate
Magnesium lauryl sulfate
Talc
Polyethylene glycol 4000
Polyethylene glycol 6000
Hydrogenated vegetable oils
Sodium lauryl sulfate

Question 29

What are disintegrants?

Answer 29

Substances added to granulation to cause tablet to break apart in aqueous environment
Reverse the effect of the binder and the compression form
May be external or internal (external when added to formed granules and internal when it is a component in the granulation mixture)
Function by swelling or reacting with water to cause disruptive forces

Question 30

What are examples of disintegrants?

Answer 30

Starch (5-20%)
Avicel (5-20%)
Alginic acid (5-10%)
Explotab (5-15%)
Kaolin (5-15%)
Veegum (5-15%)
Bentonite (5-15%)
Acid base (3-20%)

Question 31

How are colorants used?

Answer 31

Usually added to tablet formulation to increase elegance or for identification
Pastel shades are often used since these are the least likely to slow mottling
Frequently used as lakes where the dye is absorbed onto aluminium hydroxide since less likely to bleed an better uniformity
Some dyes are photosensitive and may discolour if not protected from light

Question 32

What are some colorants used?

Answer 32

Red #3 (erythrosine)
Red #40 (allura red AC)
Yellow #5 (tartrazine)
Yellow #6 (sunset yellow)
Blue #1 (brilliant blue)
Blue #2 (indigotine)
Green #3 (fast green)

Question 33

Once the granules are ready to be prepared, what happens next?

Answer 33

Excipients and drug are now put into a form with suitable flow and compression characteristics
Granulation is possibly the most important step in tableting
Several processes for producing granules are: dry granulation, wet granulation, no granulation (direct compression)

Question 34

What are the steps of wet granulation? (9)

Answer 34

Milling of drug and excipients
Mixing of milled powders
Preparation of binder
Preparation of wet mass
Screening of wet mass
Drying of granules
Screening of dry granules
Mixing with lubricant
Tablet compression

Question 35

What are the steps of dry granulation? (6)

Answer 35

Milling of drug and excipient
Mixing of milled powders
Compression into slugs
Screening of slugs
Mixing with lubricant
Tablet compression

Question 36

What are the steps of direct compression? (3)

Answer 36

Milling of drug and excipient
Mixing of milled powders
Tablet compression