The process of converting fine powders into granules is called granulation. The granulation process is used to manufacture tablets in pharmaceutical industries. Conventionally two granulation methods are used which are as follows,
- Wet granulation
- Dry granulation
In the wet granulation method solvent or binder solution is added in powders to convert powders into granules.
In dry granulation, fine powders are converted into granules by the application of pressure without addition of solvent or binder solution.
With advancements in technology many advanced granulation techniques are developed some of them are as follow,
- Hot Granulation Technique
- Foam Binder Granulation Technique
- Steam granulation technique
- Moisture activated dry granulation technique.
- Freeze Granulation technique.
- Reverse wet Granulation
- Pneumatic Dry Granulation Technique
1.0 Hot Granulation Technique
Hot granulation or hot meltable granulation technique is opposite to wet granulation method.In wet granulation method solvent or binder solution is added into fine powders and the process of drying is used to remove excessive moisture.
In hot meltable granulation technique solvent or binder solution is not added and the drying process is also eliminated. In hot meltable granulation method, a solid binder is used which melts on heat usually at 40-90°C.Commonly used binder for hot meltable granulation technique is Macrogol 6000.
Steps of Hot Metlable granulation
Following are steps of hot meltable granulation technique.
- Final Blending
In this step the ingredients are weigh according to Manufacturing Order or dispensing order to ensure exact quantities of all APIs and excipients.
All the ingredients are sieved to ensure uniform size and to remove any foreign objects like rubber band etc if mistakenly added during packaging of materials.
In mixing step API,diluent and binder are mixed in a blender to ensure uniform mixing.
For hot granulatiom technique, steam jacket high-speed mixer is used.The premixed powder which contains API, diluent and meltable binder is added into a steam-jacketed mixer and heat is applied for 4-5 minutes.Then it is mixed at high temperature to ensure proper melting and mixing of the binder. The molten binder converts the fine powers into granules.
After ensuring proper granulation the hot product is removed from the mixer in SS trays and it is cooled at temperature 20-25 °C for 6-7 hours.
When the product is cooled it is sieved through a proper mesh to produce uniform size granules.Sieve number is selected according to tablet weight and dissolution profile.
Do not sieve the granules it they are not properly cooled because if we’ll sieve hot granules it will result in sticking and picking during compression.
In this step the cooled sieved granules are mixed with remaining excipients like lubricants and the product is removed in containers after blending.Now this product is ready for compression.
2. Foam Binder Granulation Technique
Foam binder granulation technique is a modification of the wet granulation method.In wet granulation method, binder solution or solvent is added but in foam granulation technique binder solution is converted into foam and then this foam is applied to the fine powders to convert powders into granules.
Steps of Foam Binder Granulation
Following are steps of foam binder granulation technique.
- Dry mixing
- Wetting with Foam binder
- Wet sieving
- Sieving of dried Mass
- Final blending
In this step all the ingredients are weigh to ensure that materials are dispensed according to the dispensing order.
In this step materials to be granulated are sieved to ensure uniform particle size by breaking the lumps.
In this step of dry mixing materials to be granulated are mixed in a high shear or low shear mixer to ensure uniform mixing.
Wetting with Foam binder
In foam binder technique solution of binder is perepared and this binder solution is converted into foam by a foam generator. By generating foam surface area of foam is increased.This foam is then added to the fine powder to convert powders into granules.With foam binder less amount of binder is used and over wetting does not occur because foam is not absorbed by powders instead foam adhere to the surface of powders and form granules.In foam binder granulation usually aqueous binder solution is used.
The wet mass is sieved through the wet mill to increase surface area of wet granules and the wet mass is dried in FBD to remove excessive moisture.
Sieving of Dried Mass
The dried product is then sieved through the proper mesh to form uniform size granules.
In final blending step, sieved granules and remaining excipients are mixed and the product is collected in containers after blendind.Now this product is ready for compression.
3. Steam Granulation Technique
In steam granulation method we use steam in place of water.
Steps of Steam Granulation
Following are the steps of wet granulation technique,
Weigh all the materials to ensure the correct dispensing of materials.
Sieving of ingredients
All the materials to be granulated are sieved through a proper mesh to break down the lumps and to ensure uniform particle size of product.
Dry mixing ensures uniform mixing of ingredients which are to be granulated.
In this step a stream of steam is introduced into the powder mix and this steam activates the binder which converts powders into granules.
Steam is produced by a steam generator and after condensation of steam, a layer of water is formed around the granules which is removed by drying.
Excessive moisture is removed by the drying process using a suitable dryer.
Dry granules are passed through a sieve to obtain uniform size granules.
In final blending dry sieved granules are mixed with remaining excipients in the final blending step and the product is collected in containers.The product is ready for compression.
4. Moisture Activated Dry Granulation Technique(MADG)
This is also known as moist granulation technique.In this method of moist granulation,little quantity of water is added into dry mixed ingredients which activate granules formation.It is a time saving technique.
Steps Of MADG
Following are steps of moisture activated dry granulation method.
All the materials are weight according to the Manufacturing Order.
Sieving & Mixing
Materials to be granulated are sieved through a mesh to ensure uniform size and are mixed in a mixer to ensure uniform mixing.
A little amount of water is added to facilitate the granulation process. For MADG starch and cellulose-based fillers or diluents are not used because they absorb moisture and retain it.70-80% materials of MADG are added in activation stage of moist granulation.
Up to 5% of water is used as a granulating solvent.The water added converts fine powders into granules.
In this step moisture absorbing excipients like cellulose are added in moist mass after moisture activation and this absorbing material absorbs excessive moisture.No drying and wet mill sieving is required in moist granulation method.
In this stage other excipients like disintegrants and lubricants are added.After final blending product is removed in containers and is ready for compression.
5. Freeze Granulation technique
In this granulation technique, the suspension or slurry is sprayed into the liquid nitrogen.In liquid nitrogen particles of slurry or suspension are frozen into granules.The drying process is carried out by sublimation of ice.
6. Reverse Wet Granulation
In this technique, the drug and excipients are added to the solution of the binder.
Steps Of Reverse Wet Granulation
Following are steps of reverse wet granulation method.
Weighing,Sieving & Mixing
First of all, ingredients to be granulated are weight according to manufacturing order and are sieved through a mesh and then are mixed in a mixer to ensure uniform mixing.
The solution of binder in water or solvent is prepared and it is added into the high shear granulator.
The mixed dry material is added into the granulator contaning binder solutiom with continous mixing to form a wet mass.
Wet sieving and Drying
The wet mass formed is passed through the wet mill and is dried in a dryer to remove excessive moisture.
The dried mass is passed through a sieve to produce uniform size granules.
In this step the dried sieve granules are mixed with remaining excipients and after blending product is removed in containers.Now the product is ready for compression.
7. Pneumatic Dry Granulation Technique (PDGT)
Pneumatic Dry Granulation Technique is the modification of dry granulation method. It is same as conventional dry granulation method but modification is done by attachment of the pneumatic system.
Powders are compressed into powder sheets by roller compactor and then are sieved or milled by dry mill.The fine particles produced during this procedure are captured by an air system are are recycled by again passing through the roller compactor.So in this way desired size granules are produced without excessive fine.And the granules formed are ready for compression.
- lux level requirment for optical inspection.
- Use of Avicel in pharmaceutical products.
- Parts an stages of compression machine.
- ULPA filters and HEPA filters.
- Bulk density and Blender capacity calculation.
- What is Sticking and picking in tablet compression?