Tablets are one of the most widely & commonly used dosage forms which are manufactured in pharmaceutical industries & are defined as the unit solid dosage form containing excipients & active pharmaceutical ingredients.
Overview Of Tablet Manufacturing
Different types of excipients & active pharmaceutical ingredients are used to manufacture tablets using the following methods,
- Granulation Process
- Direct Compression
In the granulation process, the powders are first converted into granules & then these granules are compressed using sophisticated compression machines.
In the direct compression method of tablet manufacturing there is no need for granulation & tablets are directly compressed from the pre-mixed blend of excipients & active pharmaceutical ingredients.
After compression tablets are coated depending on the requirements, are packed & delivered to the market for use.
Image Source – Google | Image by – Senieer Resized & edited by author.
Granulation Process In Tablet Manufacturing
In this article, you will learn all about various granulation techniques which are used in pharmaceutical industries for tablet manufacturing.
The tablet granulation is a multi-step process which is performed by using different equipment depending upon the types of granulation.
What is Tablet Granulation?
Tablet granulation is the process which is used to convert powders into agglomerates or granules by the process of adding binder solution/solvent or by the use of pressure.
We can easily understand from the above definition that we can convert powders into granules by two basic methods,
- Solvent Addition
- Using Pressure
If you understand the above concept you can easily understand the whole tablet granulation process & its types.
Granulation Methods Of Tablets
Two types of tablet granulation methods are commonly used in pharmaceutical industries
- Wet Granulation
- Dry Granulation
We will discuss each method of granulation in detail based on practical experience & observations but first have a look at the basic concept of granulation.
Tablet Granulation Basic Concept
If you focus on the definition of granulation process you will find two main factors “solvent & pressure”.
These two factors are determining factors for types of granulation. As we discussed earlier there are two main granulation techniques namely wet granulation & dry granulation.
If we use solvent for agglomeration then this method is known as wet granulation & if we use pressure then this method of tablet granulation is known as dry granulation.
I’m trying to create a rhythm for readers & professionals by putting all possible questions which a reader or a professional may have in their mind so the first question which comes to mind is,
Why do we convert powders into granules?
One may ask why we use a series of steps for granulation rather than simply compressing the powders.
There are many reasons why we have to convert powders into granules, here in this article we will discuss only a brief description of logical reasoning and I will try to write a detailed article on this topic.
Follow are the main reasons for which we convert powders into granules
Powders have poor flow so we convert powders into granules to improve flow properties.
Due to the flow issue of powders, weight variation is observed during compression & granules are manufactured to overcome this issue.
Powders produce more dust & may result in high line loss.
Powders tend to segregate but granules do not.
Due to segregation, the assay & content uniformity of powders is disturbed.
Powered have low compaction properties.
Powders tend to cap or laminate but for granules this tendency is low.
Types Of Granulation
Wet granulation & dry granulation are two types of granulation and now we will discuss each type in detail.
When we discuss wet granulation, the following are the main questions which may arise in our minds.
- What is wet granulation?
- When do we use wet granulation
- Steps of wet granulation?
- The procedure of wet granulation?
Let’s discuss the above-mentioned questions one by one to learn about the wet granulation process & its implementation in pharma.
What is Wet Granulation?
The process in which powders are converted into agglomerates or granules with the help of solvent or binder solution is known as wet granulation.
As the name indicates, wet means we make our powders wet & it is done by using any suitable solvent depending upon the tablet formulation. Both aqueous or organic solvents can be used but the use of aqueous solvent (water) is encouraged if drug stability is not affected due to environmental & operator safety point of view.
When Do We Use Wet Granulation?
The first question which comes to mind is for which products we will use wet granulation & for which we will use dry granulation method?
The answer is very simple
The wet granulation technique is used to manufacture those products which are not affected or degraded by moisture or heat.
So we can say that the stability of a product plays an important role in selecting the type of granulation.
Steps Of Wet Granulation?
As we discussed earlier wet granulation is a multi-step process so it is generally consist of 8 steps which are given below,
- Pre Mixing
- Wetting or kneading
- Sieving Of Wet Mass
- Drying of Wet mass
- Sieving/Screening of dried mass
- Final Mixing or Final Blending
Read details of all the above steps in the following article.
Procedure Of Wet Granulation?
The Process of wet granulation used in pharmaceutical industries for tablet manufacturing starts with weighing all the excipients & active pharmaceutical ingredients. After checking the weight of all the materials, the next step is pre-sieving where materials according to the batch manufacturing record are sieved before pre-mixing.
All the sieved materials are then transferred to the mixer(high shear or low shear) where the process of pre-mixing is completed. When the pre-mixing step is completed, the binder solution is sprinkled over the pre-mixed materials which is uniformly mixed by impeller blades & large lumps formed are broken down with the help of a chopper mounted on the side wall of RMG or rapid mixing granulator if we are using high shear mixing granulator.
If low-shear mixers like a ribbon or plough mixer are used then large lumps are broken down manually after specified time intervals. This step of binder addition is known as the wetting or kneading process which is the most critical stage of wet granulation.
After kneading the wet mass is passed through a wet mill to increase the surface area of wet granules formed & this stage is known as the wet Sieving step of granulation.
Until now we have made our powders wet with the help of a binder solution & and a uniform wet mass is obtained having a few to many liters of organic or aqueous solvent.
Now we will have to remove the extra solvent or solution to get the required level of moisture content & for this purpose, we use the process of drying where a fluid bed dryer or a tray Dryer is used to dry the wet mass.
When our required level of LOD is achieved then this dried mass is sieved using a mill or oscillating granulator where a specified mesh is used to obtain uniform-size dried granules & this stage of wet granulation is known as dry sieving or screening of dried mass.
The dried sieved granules are transferred to the blender & are mixed with other excipients like disintegrants, colorants,glidants & lubricants depending upon the formulation.It is the last step of wet granulation known as the final blending or lubrication step of wet granulation.
Now our final blend of granules is ready for compression, it is off-loaded into containers and delivered to the storage area or the compression area depending upon the requirements.
What is Dry Granulation?
Dry granulation is the technique of converting powders into granules by using pressure.
As the name dry granulation indicates that in this process of granulation, there is no use of solvent so we prepare granules by applying pressure on the powder.
The pressure is applied by two methods either by compression machine(Slugging) or by the use of a roller compactor.
Due to the slugging process, the dry granulation method is also known as the compression granulation method or the double compression granulation method.
If someone asks to describe the double compression granulation method or compression granulation method, don’t be confused, actually he is asking about dry granulation.
When Do We Use Dry Granulation?
The dry method of granulation for tablet manufacturing is used for products which are degraded by the use of moisture or heat.
In simple words, we can say that thermolabile & moisture-sensitive products are manufactured by using dry granulation techniques.
Steps Of Dry Granulation?
The first 3 steps of dry granulation & last step are the same as that of wet granulation.The main difference is at step number 4 which in wet granulation is kneading but here is the application of pressure.
- Pre Mixing
- Application Of Pressure
- Roller Compactor
5. Screening Of Slugs
6. Final Mixing/ Blending
Procedure Of Dry Granulation?
Dry means solvent-free, as we are not using any solvent in this granulation technique so it is known as dry granulation.
It is also clear that as we are not using any solution that is why there is no need for a drying process in dry granulation.
Now the question is how we will prepare granules in dry granulation if we are not using any solvent.
To answer this question let’s have a look over the process of dry granulation.
The dry granulation method starts with weighing, sieving & then pre-mixing is done.
After pre-mixing, instead of kneading, we go towards the application of pressure where pre-mixed powders are compressed on a compression machine to form slugs.
Slugs are large-size tablets having a one-inch diameter.
When slugs are formed then the next step is crushing or screening these slugs by a multi-mill or oscillating granulator using a specified sieve to get uniform size granules.
Another technique for applying pressure is the use of a roller compactor which is also known as a chilsonator where the powder is compressed between two rotating rollers and is converted into powder sheets.These powder sheets are screened to get granules.
So by applying pressure, slug or powder sheets are formed which after screening produce granules & in this way the fine powders are converted into granules without adding solvent or heat.
After screening, these granules are mixed with remaining excipients in the same manner as in the last step of wet granulation.
After the final step of blending our blend is ready for compression.
- Granulation Defects
- Difference between wet & dry granulation?
- Advancements Granulation Techniques.
- End point determination or wet granulation.