Tablet Granulation Interview Questions

What Is Granulation?

Granulation is the process which is used for manufacturing tablets, capsules, or dry powder suspensions & is defined as follows,

The process of converting fine powders into large agglomerates or granules by using solvent, binder solution, or by the application of pressure is known as granulation.

What are the Types Of Granulation?

There are two main types of granulation which are given below,

• Wet Granulation
• Dry granulation

How Many Methods Are Used For Tablet Manufacturing?

The following three methods are used for manufacturing tablets in pharmaceutical industries,

• Wet Granulation
• Dry Granulation
• Direct Compression

Define Wet Granulation

Wet granulation is the process in which fine powders are converted into large agglomerates or granules by using a solvent or binder solution.

Define Dry Granulation

Dry granulation is the process in which fine powders are converted into granules by using pressure.

What Is the Direct Compression Method?

The direct compression method is the process that is used for those materials which have good flow and high compaction properties.

Read Details

Direct Compression Method

What are Steps Of Wet Granulation?

Following are the steps which are used during the wet granulation method of tablet manufacturing in pharma,

• Weighing
• Sieving
• Pre-Mixing 
• Wetting/Kneading/Binder addition
• Sieving Of Wet Mass
• Drying Of Wet Mass
• Sieving Of Dried Mass
• Final Mixing/Final Blending

What Are Steps Of Dry Granulation?

Following are the steps which are used for the dry granulation method of tablet manufacturing,

• Weighing
• Sieving
• Pre-Mixing 
• Slugging/Roller Compaction
• Screening
• Final Mixing/Final Blending

What Are Steps Of Direct Compression?

The following steps are used for the Direct Compression Method

• Weighing
• Sieving
• Mixing 
• Compression

Why Do We Use 03 Different Methods For Tablet Manufacturing?

All products can not be manufactured by using a single method because each method has some limitations so we use any of the three methods depending on the product’s nature.

For Which Products Do We Use the Wet Granulation Process?

A wet granulation process is used for those products which are not degraded by moisture or heat.

For Which Products Do We Use the Dry Granulation Process?

The dry granulation method is used for heat-sensitive & moisture-sensitive products or in simple words for thermolabile products.

For Which Products Do We Use Direct Compression Method?

The direct compression method is used for those materials which have the following characteristics,

• Good Flow Properties
• Good Compaction
• Low Dose Products

What Is Kneading?

Kneading is the step of wet granulation in which we add solvent or binder solution to the pre-mixed fine powders to form a wet mass.

How Granules Are Formed In Wet Granulation?

In wet granulation fine powders are converted into wet mass during the kneading process & then this wet mass is sieved & dried. After drying the dried mass is again sieved to get uniform-sized granules.

How Granules Are Formed In Dry Granulation?

As we know, the dry granulation method is used for thermolabile products so we can not use solvent or binder solution means kneading is not done during the dry granulation process, so a common question comes to mind which is,

“How do we convert powders into granules by the process of dry granulation”? 

When I ask this question to various professionals who have no experience with granulation, about 90% of people say it is done by the sieving process.

Then I ask if we sieve powders, they are not converted into granules, only particle size is reduced.

The correct answer is by application of pressure we convert powders into slugs or powder sheets and later by screening slugs or powder sheets we get granules.

Why Do We Perform Pre-Sieving Step In Granulation?

Sieving before mixing is done in wet & dry granulation because of the following,

• To break large lumps.
• To get uniform particle size.
• To remove any foreign particles.
• To Remove any foreign Material.

Why Do We Perform Wet Sieving In Wet Granulation Method?

Wet sieving in the wet granulation method is performed to break large lumps of wet mass  & to increase surface area. This increase in surface area facilitates the drying process.

Why Do We Manufacture Granules?

Powders are converted into granules because of the following main reasons,

• To Improve Flow
• To increase compaction
• To prevent segregation.
• To get better content uniformity & assay.
• To prevent line loss due to a dusty environment 
• Powders are elastic & tend to laminate or cap but granules are plastic.

Write Down Defects Of Granulation?

The following main defects can be observed during the granulation process.

• Over Wetting
• Under Wetting
• Over Drying 
• Under Drying
• Excessive Fine
• Segregation
• Assay Issue

What Is the Sieve Selection Criteria?

The selection of sieve for oscillating granulator or dry mill depends on the following,

• Required Granules Size
• Weight Of Tablet
• Disintegration Time
• Dissolution Profile
  

What Are Factors Affecting Kneading?

The following factors may affect the kneading process,

• Solvent/Binder Solution Quantity
• Binder Addition Time
• Kneading Time
• Speed Of Impeller Blades
• Speed Of Chopper Blades

Name of Equipment Used For Kneading?

• RMG
• Spiral Mixer
• Plough Mixer
• Diosna Mixer

What Is RMG?

RMG stands for Rapid Mixing Granulator and is the equipment that is used for the wet granulation process.

It belongs to the class of mixers known as High Shear Mixers.

What Are the Components Of RMG?

Following are the main components or parts of the rapid mixing granulator or RMG,

• Mixing Bowl
• Impeller Blades
• Chopper Blades
• Binder Addition Hopper
• Breathing Filter
• View Port
• Discharging Port
• Pneumatic Sealed Lid
• HMI

A Wet mill is also attached with RMG for wet sieving of wet mass.

How RMG Works?

Powders to be mixed are added into a mixing bowl of RMG & are mixed with the solvent with the help of impeller blades. The chopper Breaks down large lumps & later this wet mass is passed through the wet mill to get a wet sieved mass.

Read 

Details Of RMG

What Is a Spiral Mixer?

A spiral mixer is also used for kneading purposes during wet granulation & it belongs to the class of mixers known as low shear Mixers.A spiral mixer is also known as ribbon mixer.

Which Equipment is Used For the Drying Process?

Products manufactured by wet granulation processes in pharmaceutical industries are dried by using one of the following.

• Tray Dryers
• Fluid Bed Dryers (FBD)

What Is Working Principle Of FBD?

FBD works on the principle of fluidization in which the settling velocity of particles is less than the air-carrying capacity of granules.

What Is Candle Filter?

The candle filter is the cloth filter used in FBD during the drying process. It has finger-like or candle-like large hollow pockets so known as finger filters or candle filters.

What Are The Factors Affecting the Drying Process?

The following are the main factors that may affect the drying process of wet granulated products using FBD

• Drying Temperature
• Drying Time
• Product Trolley Load
• Fan Motor Speed

Which Inprocess Test Is Performed During Wet Granulation?

LOD or loss on drying.

Read About FBD

Fluid Bed Dryer Working 

Other Names Of Dry Granulation?

The other names used for dry granulation method are,

• Compression Granulation
• Double Compression Method
• Slugging Method
• Roller Compaction Method

What is a Roller Compactor?

A Roller compactor is used to form paper sheets during dry granulation. As the name indicates it consists of two rolls that rotate and apply pressure over powder & form paper sheets. These powder sheets are then broken down by the dry mill & screened to get granules.

What is Chilsonator?

The roller compactor is also known as a chilsonator.

What Is Slugging?

Slugging is the step of dry granulation in which powders are compressed into large-size tablets by using large flat-face punches.

What Is Slug?

A slug is a large tablet 2 inches in diameter.

Example Of Direct Compression?

Powders having crystalline form & good compaction properties are compressed using the direct compression method.

Example

• Aspirin

Excipient Classes Used For Granulation?

The following main classes of excipients are used for manufacturing OSD depending on the nature of the formulation.

• Diluents
• Binders
• Disintegrants
• Lubricants
• Glidents
• Colorants
• Flavourants

Read About

Classification Of Excipients

What Is OSD?

OSD represents the Oral Solid Dosage Form.

Stages Of Granules Growth?

Following are 4 stages of Granules growth during the kneading process,

• Pendular
• Funicular
• Capillary
• Droplet

Equipment For Wet Granulation?

The following equipment may be used for manufacturing of granules by wet granulation method

• Sifter/Sieves
• RMG/Spiral Mixer
• Wet Mill
• FBD/Tray Dryer
• Oscillating Granulator
• Dry Mill/Multi Mill
• Double Cone Blender/Bin Blender

Read Details

Equipment Used For Wet Granulation

Equipment For Dry Granulation?

The following equipment may be used for manufacturing of granules by wet granulation method

• Sifter/Sieves
• Double Cone Blender/Bin Blender/Spiral Mixer
• Roller Compactor/Compression Machine
• Oscillating Granulator
• Dry Mill/Multi Mill/Fitz Mill

Equipment For Direct compression?

The following equipment may be used for Direct Compression

• Sifter/Sieves
• Double Cone Blender/Bin Blender/Spiral Mixer

Advanced Granulation Techniques?

Following are the advanced granulation techniques which are also used for manufacturing OSD products in Pharmaceutical industries,

• Hot Granulation Technique
• Foam Binder Granulation
• Steam Granulation
• Reverse Wet Granulation
• Freeze Granulation 
• Moisture Activated Dry Granulation
• Pneumatic Dry Granulation

Read Details

Advance Granulation Techniques

What Tp Check During Line Clearance?

 The production pharmacist must check the following during line clearance,

• The area is properly cleaned & labeled.
• Equipment Cleaning & labeling
• No leftover of previous product
• Temperature & Humidity level
• Differential pressure
• Balance verification
• Signed BMR & Manufacturing Order is available.
• Verification of lots & weight of every material 

Read Details

Line Clearance In Pharmaceutical Industries

What Will be The Drawback Of Over-wetting?

A common question is asked: what will happen if our product is over-wet during the kneading step?

The possible effects may be as given below,

• Wet Mill Sieve Clogging 
• Hard Granules Will be produced After Drying
• Difficulty in Dry Sieving
• Sieve damage during dry sieving due to hard granules
• Production Of Less Fine Which may promote capping or lamination.
• Prolong D.T 
• Retarded Dissolution Profile 
  

What Will be The Drawback Of Under-Wetting?

• Weak Granules
• Production Of More Fine During Drying.
• Increased Line Loss During Drying.
• Dusty Environment During Dry Sieving.
• Segregation During Final Blending.
• Capping Or lamination Due to more fine. 
• Flow Problems during Compression.
• Weight Variation 

What Will Be The Drawback Of Over Drying?

• Excessive Fine May Produce
• Fragile Granules
• Capping
• Lamination
• Weight Variation

What Will Be The Drawback Of Under-Drying?

• High Moisture Content
• Sticking
• Picking
• Rathole
• Weight Variation

What Is Double Disintegration?

When a disintegrant or super disintegrant is used during both intragranular & extra granular stages it is known as the Double Disintegration Phenomenon.

What Is Binder Activation?

Binder activation is a general term used during the wet granulation method in which we do not prepare binder solution rather we mix our binder in dry form during the pre-mixing stage & then in the kneading step we only add water or organic solvent to give a binding effect.

As the binder in dry form is activated later on by solvent, this process is known as a Binder Activation Method.

What Is Case Hardening?

Localized over-wetting may produce large lumps and binder may entrap if these large lumps are not properly broken down. During drying, if a high temperature is applied at the start it may dry the granules from the outside but inside, the binder remains wet. This phenomenon is known as case hardening.

Case Hardening may result in sticking or picking during the compression process.

Read Details

Reasons For Tablet Sticking And Picking]

Binder Quantity VS Dissolution?

If the amount of binder in wet granulation is very high it will result in strong bounding of granules so drug release will be very slow & dissolution profile will be low.

If a very less quantity of binder is used during wet granulation it will result in weak bounding & will result in capping or low hardness friable tablets.

What Is the Optimum Blending Time Of Granules With Lubricants?

Granules should be mixed with lubricants for 3 to 5 minutes. The mixing time with lubricants should not exceed 5 minutes.

Drawbacks Of The Lubricants Over-Mixing?

If lubricants are used in excessive amounts or blending time with lubricants is increased it may result in the following defects,

• Increased Disintegration Time
• Low Dissolution Profile
• Low Hardness
• Tablet Capping
• Tablet Lamination

Read Details

Lubricants Used In Pharmaceutical Industry

Also, Read

1. Quality Assurance Interview Questions
2. Pharmaceutical Questions and Answers.
3. 100 MCQs to revise your pharmaceutical knowledge.
4. Potency calculation of Active Pharmaceutical Ingredient.
5. Wet Granulation and Dry Granulation
6. Lubricants Effect On Disintegration