Solid Dosage Forms: Processing of Tablets

What is a tablet?

A compressed powder consisting of drug and inert excipients

What are the advantages of tablets?

• Accurate dosage / minimum variability

• Convenience

• Greater physiochemical stability than liquid preparations

• Rate of release of drug can be tailored

• Mass production

• Simple and cost effective

• Patient acceptability

What are the disadvantages of tablets?

• Swallowing issues

• Difficulty in preparing certain formulations

• Poorly wetting and low solubility drugs

• Bitter taste

• Oxygen and moisture sensitivity requiring coating of certain tablets

What are the essential properties of tablets?

• Accurate and uniform dose

• Uniform in weight, appearance, and size/shape

• Recognisable and ideally patentable shape

• Must withstand stresses of processing and handling

• Appropriate and reproducible dissolution rate

• Moisture and temperature stability

For particulate systems to be made into tablets, what 3 vital properties are required?

1. The particles must be sufficiently free flowing

2. The particles, when subjected to a force, cohere to form a compact of adequate strength

3. Adhesion of the tablet must be avoided

Why are excipients required in tablets?

APIs don’t usually have all the essential properties

What are the steps of making a tablet?

1. Weighing

2. Dry mixing

3. Granulation

4. Tableting

5. QA check

6. Dissolution

7. Coating

8. QC check

How do tablet machines work?

• Powder is filled into a die to a specific depth.

• The formulation is compressed between two punches to form a tablet.

• The upper punch is removed to end compression.

• The lower punch moves upward to eject the tablet.

What are the two types of tablet presses?

• Single (or eccentric) punch pressures

• Rotary presses

The compression of a powder bed can be defined by 3 stages. What are the stages?

Stage 1: Rearrangement of the powder bed upon application of a stress

Stage 2: Deformation of the powders due to the applied stress

Stage 3: Bonding of the compressed powders

Stage 1 - Rearrangement

At low pressure, the powder bed becomes more compact (densification).

Particles move and rearrange to reduce empty spaces between them.

How much densification occurs depends on particle size distribution and friction between particles.

As pressure increases further, particles can no longer move past each other, so they begin to deform instead.

Stage 2 - Deformation

• Once particles are packed tightly together, empty spaces can no longer be filled.

• Further compression causes the particles to deform.

• Particles may undergo:

  • elastic deformation

  • plastic deformation

  • fragmentation

• This can permanently change the shape of the material.

• The type of deformation depends on the physicochemical and mechanical properties of the powder.

What materials caused plastic deformation?

Stearic acid, starch

What materials cause fragmentation?

Sucrose, lactose

Stage 3 - Bonding

When enough pressure is applied and the particles deform, interparticle bonding occurs, producing a tablet

What is direct compression?

A tablet manufacturing method where powders are compressed directly into tablets without first being granulated.

What is dry mixing?

Dry mixing is the process of blending powdered ingredients together without using any liquid.

What are the main steps in direct compression tablet manufacture?

1. Ensure the active ingredient has a suitable particle size.

2. Dry mix the API with excipients such as fillers, lubricants, flow aids, and disintegrants.

3. Compress the powder blend directly into tablets.

What is granulation?

The process by which primary powder particles adhere to form large multi-particulate entities called granules

How are bonds formed?

Bonds are formed either by compression or via a binding agent

Is powder more or less difficult to compress into a tablet than granulated materials?

More difficult

Why should we granulate?

To produce uniform particles with good flow properties, increased compressibility, resistance to agglomeration and segregation, and reduction in dusting.

What does the granulation process produce?

Large agglomerates (200-400 micrometers)

What is added for compressibility?

Plasticisers and binders

What is wet granulation?

A tablet manufacturing process where powders are mixed with a liquid binder to form granules before compression into tablets.

What is the role of the binder in wet granulation?

• Helps particles stick together

• Forms granules for better flow and compression

What are the disadvantages of wet granulation?

• Time-consuming and labour-intensive

• Expensive

• Drug exposed to extensive processing (heat/moisture)

Which solvents are used in pharmaceutical granulation and why are options limited?

Solvents: water, ethanol, isopropanol

• Limited choice because the solvent cannot be completely removed during drying

What is dry granulation (slugging)?

Dry granulation is a tablet manufacturing method used when powders cannot be directly compressed because of poor flow or compression properties. It is also useful for heat or moisture sensitive drugs, like aspirins.

What are the steps in dry granulation (slugging)?

1. Powders are mixed and pre-compressed at high pressure to form large slugs.

2. The slugs are ground into granules of uniform size.

3. The granules are blended with excipients if needed.

4. The final blend is compressed into tablets.

What are the advantages of dry granulation Vs wet granulation?

• Economical

• Less equipment and space than wet granulation

• Eliminate addition of moisture and heat

• Can cope with a wide range of materials

• Process is easily scaled up

• Mechanical strength of the product is uniform