The Process of Dry Granulation and Its Significance in The Pharmaceutical Industry

Most of the manufacturing methods used in the pharmaceutical industry have features such as speed, cost-effectiveness, and safety. These are some characteristics of dry granulation, a technique used to manufacture tablets from dry powder without using water. In this article, you will learn all about this process, and how it works.

What is Dry Granulation?

There are many definitions of this process. However, all of them revolve around one singular idea — producing granules from dry powder without adding any water. Dry granulation relies on compaction and compression techniques to pack the dry powder in a way that it will not crumble easily. This is quite challenging, but the machines used for dry granulation are effective.

The reason why this method exists is to aid in the manufacturing of granules that are sensitive to moisture or any solvents in the forming process. 

Dry granulation techniques are carried out using specific machines that can produce the necessary pressure and compression to form the granules. Also, these machines are required to dispense the right amount of powder for granule formation.

One of the major challenges of dry granulation is that sometimes the dry powder may not flow at a constant rate, thereby affecting the granulation. Specifically, the lack of a uniform flow rate could potentially lead to granules with varying weights and shapes. These challenges will become clearer as you learn more about how this process occurs.

The Dry Granulation Process 

Dry granulation is a systematic process. That means it occurs through a series of steps starting from the preparation of the material to the final blending of the granules. In each step, there are control measures used to ensure that the technique works as expected. Let us learn more about these steps.

Preparing the Material

One thing to keep in mind is that dry granulation is not only used in the pharmaceutical industry but also across multiple industries. It is just that pharma is among the pioneers of the technique. Also, this article primarily focuses on dry granulation in the pharmaceutical industry

The process starts with the preparation of the dry powder that will be fed into the compressor or compaction unit. A lot can go on in this preparation. 

To start with, the active ingredient in the powder is mixed with excipients — inert compounds that facilitate dry granulation. 

After the active ingredients and the excipients are mixed, they are blended in special grinders to produce a homogeneous powder. This powder is then fed into the specific machine for the agglomeration to occur.

Feeding the Compaction Unit

Compaction is defined as the use of force to pack matter tightly. This is the step in the process that matters the most. 

Dry granulation can be carried out using various techniques. The most widely used in pharma are slugging and roller compaction.

Slugging and roller compaction are initial steps that produce large tablets that will then be milled in the next step to produce the individual granules. In slugging, the large tablets are typically referred to as slugs. They measure about 20 mm in diameter and 15 mm in thickness. 

Roller compactors form long ribbons using two rollers that rotate in opposite directions. We will elaborate more about how this works in another section of the article.

Milling Process

The actual granulation of the dry powder occurs in this step. Milling involves the breakdown of the slug and the long ribbons into small granules.

In most cases, the machine that mills the compacted powder into granules is the same that makes the ribbons and slugs. This means that the machines usually have multiple functions. This design decision is made to maximize efficiency and promote productivity.

Final Blending

At the milling step, most of the work is usually done. However, in some cases, a final blend is needed. This blend can involve the addition of other excipients in the granules. It is meant to improve the qualities of the granule compounds.

Types of Dry Granulation Techniques

Dry granulation is a technique that is widely practiced in different industries. As such, you would expect that various techniques are used. All these methods have the same goal of making granules from powder without involving solvents or liquids. Let us discuss some of the common dry granulation techniques and the machines involved.

Types of Dry Granulation Techniques 

When dry granulation was invented, some techniques were adopted immediately and became an industry standard. Roller compaction is one of these techniques. 

Pneumatic dry granulation was developed in a bid to improve the current roller compaction as a dry granulation technique. This method has technical improvements that make the original method much more efficient.

Particularly, pneumatic dry granulation improves roller compaction by increasing the flow of the feedstock in the compactor. This means that there will be more uniform granules and a high processing volume and speed.

Slugging 

In this technique, a compression machine is used to prepare the slugs. Previously, we defined these slugs but we did not explain how they are made. Slugs are made in a multi-step process that turns dry powder into granules.

The slugging technique is utterly time-consuming since it involves a lot of steps. Due to this, the process ends up becoming ineffective and unreliable for large production volumes. Also, this technique has a lot of waste and it requires large space.

Dry Mixing 

This type of dry granulation technique only involves a minimum of four steps. These four steps take place in sequence starting with sifting, mixing, final blending, and lastly compression. In each step, there are control steps that are carried out by technicians to ensure that the granules come out as expected.

The success of the dry mixing technique depends on factors such as the quality of the active ingredient and the excipients have to be in excellent condition. 

Roller Compaction

This is one of the best dry granulation techniques. It involves the use of rollers to transform the dry powder into ribbons that are then granulated by a roller compaction machine. This technique is popular and widely used for its high production volume and reliability.

Characteristics of Dry Granules

The end products of dry granulation techniques are known as granules. These small or large solid dosages have some notable characteristics that define them. Here are some of these characteristics and features.

Porous and Highly Compressible

When the roller or compactor machines apply compression force on the dry powder, they form granules that have high porosity. Porosity means that there is a lot of space between the powder particles making up the granule. This means that the granule can absorb water or other liquids quite easily. This is why granules have fast disintegration.

Taste Masking

During dry granulation, the granules are usually coated with a polymer that masks the taste of the granule, making it hard for the granules to lose taste.

Taste masking polymers are used to make this happen. It is also applied using a dry coating technique that is similar to the granulation method. Taste masking is an essential step in the process of making dry granules.

Fast Disintegration

When a solid substance loses its cohesion and breaks down, it is used to disintegrate. This is a characteristic that is quite often observed with dry granules. The fast disintegration of granules is advantageous, especially for medicinal tablets. This is because they will break down fast in the stomach. 

Advantages of Dry Granulation

As one of the most common granulation methods, dry granulation has several advantages. This is what makes it preferred to wet granulation. Some of these benefits include;

Cost-effective Granulation Method

The cost of manufacturing granules through dry granulation is usually quite low. This means that the process is cost-effective. Another aspect that shows the cost-effectiveness of dry granulation is the high production volume of both roller compactors and slugging machines. 

Flexible for Small and Large-scale Production

Most large-scale manufacturing systems are unable to cope with low-volume production for various reasons. For dry granulation, it is completely different. Whether you are planning to manufacture dry granules for personal or commercial use, dry granulation is perfectly suited to handle this process.

The Equipment Takes up a Small Space

Dry granulation machines, for example, the roller compactor, are sizeable compared to what it is capable of manufacturing. One of the reasons for this observation is that the end product and the feedstock are usually small in size. 

Involves Fewer Unit Processes 

Essentially, there are at most four steps in the dry granulation technique. We discussed these steps in a previous section where we talked about the dry granulation process. 

The advantage of this technique having few processes reflect on the production volume of the dry granules. In other words, the manufacturer can produce large quantities of granules. In business, an increase in production volume automatically means more revenue for the business.

Produces Stable Products

The stability of products is quite essential, especially in the pharmaceutical industry. In this case, stability means the ability of the granules to retain shape and size. While some of the dry granules crumble easily, most of them manage to retain their shape under stressful conditions.

Excellent for Moisture-sensitive Drugs

Dry granulation is an excellent manufacturing technique for drugs that are sensitive to moisture. This includes drugs that have active elements that react poorly when they come into contact with moisture content. 

Disadvantages of the Dry Granulation Technique

Whereas dry granulation is an almost perfect technique for producing solid granules without using water, it has some flaws. Some of the common disadvantages of this technique involve the final product and not the process itself. The following are some of them;

Possible Cross-contamination from Dust Produced 

The process of dry granulation produces dust as it forms the granules. The dust comes off since there is no water or liquid to prevent dust particles from escaping during the compression. This dust can cause cross-contamination if it finds its way back into the machine. As such, control measures are needed to eradicate this problem.

Tablets Produced Might Easily Crumble

Provided that the granules that are made from dry granulation are highly porous, there is a high possibility of them crumbling. Additionally, the roller compaction machine has subpar flow characteristics which affect the nature of the granules. Specifically, the granules might end up in varying sizes and shapes, which eventually means poor stability.

Not Suitable for Some Products

The main reason why the dry granulation technique exists is to cater to products that cannot be granulated without water. On the other hand, those that require water can be easily manufactured using the alternative technique — wet granulation.

Challenges of Dry Granulation 

Apart from the disadvantages that are observed with this technique, there are specific challenges that can be considered setbacks when you are considering dry granulation as a production technique for solid granules. Some of these setbacks include;

High-quality Requirement of the Granules 

Industries like pharma have high standards that they expect of the products. This is because of the universal use of these products. In that case, one of these expectations is for the granules to be perfect. However, it is rarely the case and that could have negative implications on the perception of products made through dry granulation.

Non-uniformity in Granule Size

The size of dry granules from all types of dry granulation techniques varies. This variance in size can result in poor reception by the end user. For the manufacturer, this could have a negative implication on the business as well. For instance, the granules could be thought of as sub-standard by customers who are not aware of this challenge.

Loss of Compatibility 

The ability to remain compact of dry granules is a challenge. Compared to granules made from wet granulation, this process results in products that can easily crumble or lose cohesion. This means that the granules can end up in powdery form after some time. This is challenging because it points to the inferiority of the technique.

Conclusion 

As a leading technique for making granules, dry granulation makes it possible to assemble powdered substances into sizeable tablets for various uses. This technique has its strengths and weaknesses. However, it has proven to be reliable and efficient. Until a better method is invented, dry granulation will be relied upon for a long in several industries. 

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