Tabs and Capsules/ Dissolution and Liberation

What are the main advantages of tablets?

They are easy to use, portable, and provide accurate dosing.

What are the main types of tablets?

Compressed, coated, sublingual, chewable, tablet triturates, and vaginal tablets.

How are compressed tablets made?

By compressing granules made from powder particles into a definite shape.

What ingredients are found in compressed tablets?

Active ingredient(s) and inactive ingredients( make up most of the tablet)

What do inactive ingredients do in a compressed tablet?

They hold the tablet together until swallowed, absorb gastric juice, help the tablet disintegrate, and help drug particles dissolve.

What is the role of a diluent (filler) in a tablet?

They add bulk to help create the desired tablet shape.

What is the role of a binder (adhesive) in a tablet?

It makes particles stick together, helps form granules, and maintains tablet shape.

What is the role of a disintegrant in a tablet?

They promote tablet breakup after administration.

What is the role of a glidant(lubricants)?

It improves the flow of granules into the tablet die before compression.

What are tablet diluents?

Inert ingredients with no pharmacologic activity.

What standards must tablet diluents meet?

FDA purity standards and Good Manufacturing Practices (GMPs).

What are common tablet diluents?

Dicalcium phosphate, calcium sulfate, lactose, cellulose, kaolin, mannitol, starch, and glucose.

What are tablet binders (granulators)?

Ingredients that help tablet particles stick together and form granules.

What are common tablet binders?

Starch, gelatin, sugars, acacia, sodium alginate, CMC, methylcellulose, polyvinylpyrrolidone, Veegum, and some waxes.

What are examples of tablet lubricants?

Sodium benzoate, leucine, Carbowax 4000, and magnesium lauryl sulfate.

What are common tablet glidants?

Colloidal silicon dioxide and sometimes talc.

What are common tablet disintegrants?

Starches, clays, celluloses, algins, and gums.

How can flavor be added to tablets?

By using a sweet filler such as sucrose or a sweetener such as aspartame.

Why are colorants added to tablets?

For appearance, drug identification, and to assess how well ingredients were mixed.

What are FDA-approved tablet colorants called

FD&C colors.

How does sugar coating affect a tablet?

It masks bad taste, improves appearance, and may increase tablet size by about 50%.

How do film-coated tablets compare with sugar-coated tablets?

They are more durable and less bulky.

What happens to film-coated tablets in the stomach?

The polymer coating disintegrates in gastric juices.

What is the purpose of an enteric coating?

It prevents dissolution in the acidic stomach and allows dissolution in the small intestine.

Why are enteric-coated tablets useful?

They protect the stomach from irritating drugs and protect drugs that should not dissolve in the stomach; mainly for geriatric patients

Where are sublingual and buccal tablets placed?

Sublingual tablets go under the tongue; buccal tablets go in the cheek pouch.

How are drugs from sublingual and buccal tablets absorbed?

Through the oral mucosa.

When are sublingual or buccal tablets useful?

When a drug is destroyed by gastric juice or needs a rapid onset.

What are the three main methods of preparing compressed tablets?

Wet granulation, dry granulation, and direct compression.

What is the first step of wet granulation?

Weigh and blend the active ingredient with disintegrants and fillers; grinder blades may be used to reduce particle size.

What is added during the second step of wet granulation?

A liquid binder, often a 10%-20% corn starch slurry, to form wet granules.

When should dry granulation be used instead of wet granulation?

When the drug is adversely affected by moisture.

What happens in the third step of wet granulation

The wet mass is screened into granules, spread onto trays, and prepared for drying.

What is fluidization during wet granulation?

Drying granules by suspending and moving them in warm air.

What is dry granulation?

Tablet-making method that uses no moisture.

How are powders processed during dry granulation?

They are blended, slugged or rolled, crushed, sieved, mixed with lubricant, then compressed.

What properties are needed for direct compression?

The materials must flow freely and have cohesive properties.

What tablet specifications and characteristics are commonly evaluated?

Tablet hardness, thickness, disintegration, and dissolution.

What is tablet friability?

The tendency of a tablet to break when exposed to stress.

Which USP chapter covers tablet friability?

USP Chapter 1216.

Which USP chapter covers tablet breaking force?

USP Chapter 1217.

What should tablet hardness protect against?

Chipping, abrasion, and breakage.

Why are some tablets intentionally made hard?

To make them dissolve more slowly.

How much pressure may compressed tablets be exposed to during manufacturing?

Up to 40,000 lb (20 tons).

How is tablet hardness monitored for quality?

It is tested with instruments periodically and randomly throughout manufacturing batches.

Why is tablet thickness tested during manufacturing?

To ensure quality; it is tested periodically and randomly within batches.

Can tablet thickness change even if tablet weight does not change?

Yes. Changes in compression can change thickness without changing weight.

Why can changes in tablet thickness be a problem?

They may clog automatic tablet-counting devices.

What tablet-thickness variation is allowed by caliper measurement?

Plus or minus 5%.

What instrument is used to measure tablet thickness?

A caliper.

What is dissolution?

The process of the active ingredient dissolving in fluid at its absorption site.

Why must most tablets disintegrate?

So the active ingredient can be released into gastric fluid and then dissolve.d

How is tablet disintegration tested?

With USP in vitro disintegration testing.

What is usually inside a swallowed-whole capsule?

Free-flowing powder.

Which capsules are designed to be opened?

Capsules that contain sprinkles or beads.

What are hard gelatin capsules made of?

Gelatin, sugar, water, and colorants.

Where does gelatin come from?

ollagen from animal connective tissue and bones.

How does gelatin behave in water?

It is insoluble in cold water but soluble in hot water.

What happens to gelatin capsules in gastric fluid?

The gelatin is digested and absorbed.

What are the two parts of a hard gelatin capsule?

A longer body and a shorter cap.

How are hard gelatin capsule shells usually manufactured?

By dipping thin metal rods into gelatin solution and allowing it to cool.

How does capsule size numbering work?

A higher capsule number means a smaller capsule.

Why are hard gelatin capsules banded?

To make them tamper-evident.

What makes a soft gelatin capsule flexible?

Adding glycerin or sorbitol to the gelatin mixture.

What types of contents are usually placed in soft gelatin capsules?

Suspensions, liquids, oils, alcohols, and esters.

Are soft gelatin capsules usually compounded in pharmacies?

No; they require elaborate manufacturing equipment.

How are soft gelatin capsules basically made?

Liquid medication is placed between warm gelatin sheets, then pressed with a mold.

What must most dosage forms do near the absorption site?

Disintegrate and dissolve.

Which dosage form does not need to dissolve first?

A solution, because the drug is already dissolved.

What does the Noyes-Whitney model describe?

How solid drug particles dissolve.

According to the diffusion-layer model, what controls the dissolution rate?

Diffusion through the thin saturated layer surrounding each solid particle.

What is a sink condition?

A condition in which the drug is absorbed as soon as it dissolves.

Why is dissolution testing performed?

To ensure consistent drug release and batch-to-batch reproducibility.

Does USP dissolution testing vary by dosage form?

Yes; different methods are used for uncoated, coated, and enteric-coated tablets.

What factors affect drug dissolution?

Particle size and surface area, ionization, drug formulation, gastric emptying, and intestinal transit time.

How does particle size affect surface area?

Smaller particles have a larger surface area.

Why is particle size especially important for poorly soluble drugs?

Reducing particle size can help them dissolve faster.

What is micronization?

Ultra-milling drug particles to greatly increase surface area.

How do salt forms of weak acids and weak bases compare with their unionized forms?

Salt forms are usually more water-soluble.

What are the approximate pH values of the stomach and small intestine?

Stomach: about pH 3; duodenum/small intestine: about pH 8.

When a drug’s pKa equals the environmental pH, what is the ionized-to-unionized ratio?

1:1.

What happens to a weak acid when pH decreases by one unit?

The unionized form increases 10-fold compared with the ionized form.

Are weak acids more or less soluble in the acidic stomach?

Less soluble, because more is in the unionized form.

What happens to a weak base when pH decreases by one unit?

The ionized form increases 10-fold compared with the unionized form.

Are weak bases more or less soluble in the acidic stomach?

More soluble, because more is in the ionized form.

How do disintegrants improve drug dissolution?

They swell and break the dosage form open, helping release drug particles.

How can lubricants affect dissolution?

They may slow it by creating a hydrophobic film around particles.

How can gastric emptying time affect dissolution?

It affects how much drug dissolves before entering the small intestine.

How fast can gastric emptying occur?

As fast as 15 minutes, but it may take over 2 hours.

How does food affect gastric emptying time?

Gastric emptying is faster when fasting and slower when food is present.

What is liberation?

The release of a drug from its dosage form before absorption.

What must happen after a drug is liberated from its dosage form?

The drug particles must dissolve in body fluids before they can be absorbed.