Tableting Granulation - How it works

LFA Machines

6 Dec 201904:27

Summary

TLDRThis video from LFA explores granulation in pharmaceutical tablet production, highlighting three key reasons: improving flowability, compressibility, and API distribution. It explains the angle of repose test for assessing flowability and the option of direct compression for sensitive APIs. The video delves into dry and wet granulation methods, including slugging, roller compaction, and fluid bed granulation, emphasizing the importance of milling for granule size standardization. It concludes with the addition of lubricants for easier tablet pressing and offers resources for further information.

Takeaways

🌟 Granulation is a process used to improve the flowability, compressibility, and uniform distribution of the active pharmaceutical ingredient (API) in a formulation.
📏 The angle of repose is a key test to determine the flowability of a powder; a low angle indicates good flowability, while a high angle suggests the need for granulation.
💊 Direct compression is a cost-efficient method for tableting where a formulation can be compressed without granulation, suitable for heat and moisture-sensitive APIs.
🔄 Mix validation is crucial to ensure the correct and consistent mixing of the tablet formulation, especially when direct compression is used.
🌡️ Dry granulation is preferred when a formulation is sensitive to moisture or heat, and it involves combining granules without the need for any liquid.
🔩 Slugging is a technique where large tablets are formed and then granulated to improve flowability before final compression.
🌀 Roller compaction is a method where a formulation is compacted into a ribbon by rollers and then granulated to create the desired granule size.
💧 Wet granulation involves the use of a binder in a liquid solution or suspension to cause aggregation of particles and improve flowability.
🌬️ Fluid bed granulation is a form of wet granulation where hot air and binder spraying within a unit help form granules by creating bridges between particles.
⚙️ After granulation, milling is necessary to standardize the granule size distribution, and lubricants are added to facilitate easier flow through the tablet press.

Q & A

What are the three main reasons for granulation in pharmaceutical formulation?
-The three main reasons for granulation in pharmaceutical formulation are to improve the flowability of the formulation, to make the formulation more compressible, and to ensure a consistent spread of the active pharmaceutical ingredient (API) throughout the formulation.
How can you test the flowability of a tablet formulation?
-The flowability of a tablet formulation can be tested by measuring the angle of repose. A small angle indicates good flowability, which is suitable for direct compression, while a high angle suggests that granulation is needed as the formulation may not flow well and could cause issues like arching, bridging, or rat holing during tablet compression.
What is direct compression in tableting and why is it cost-efficient?
-Direct compression in tableting is a process where the API and excipients are mixed and then directly compressed into tablets without any further steps like granulation. It is cost-efficient because it simplifies the manufacturing process, reducing the need for additional equipment and steps, and is also suitable for sensitive APIs that may be affected by heat and moisture.
Why is mix validation important in tablet formulation?
-Mix validation is important in tablet formulation to ensure that the API and other components have been mixed correctly and uniformly. This prevents issues like segregation and ensures consistent dosage and quality of the final product.
What is dry granulation and when is it used?
-Dry granulation is a process that combines granules without the need for any liquid. It is generally used when the formulation is sensitive to moisture or heat, as it avoids the use of solvents that could degrade the API or cause other issues.
What is slugging and how does it relate to dry granulation?
-Slugging is a process where a tablet press is used to form large tablets that vary in weight due to poor flowability of the formulation. These 'slugs' are then passed through a granulator to break them down into granules, which are then compressed again to form the final tablets. This is related to dry granulation as it is an alternative method to improve the flowability of the formulation.
What is roller compaction and how does it differ from other granulation methods?
-Roller compaction is a process where the formulation is fed through a roller compactor, where two rollers compact the powder to form a ribbon. This ribbon then passes through a granulator where it is forced against a mesh to create granules of the desired size. It differs from other granulation methods as it uses mechanical pressure to form the ribbon before granulation, and it's often used for formulations that are sensitive to the addition of liquids.
How does wet granulation work and what is its purpose?
-Wet granulation involves the use of an adhesive, often a binder, which is incorporated into the formulation as a solution or suspension in a suitable liquid. The purpose of wet granulation is to cause aggregation of particles, forming solid bridges between them to create granules of a consistent size. This process is popular as it is applicable to most formulations and can improve the flowability and compressibility of the final product.
What is the role of a fluid bed granulator in wet granulation?
-A fluid bed granulator is used in wet granulation to facilitate the binding of granules. Hot air is fed into the bed, lifting the granules while they are sprayed with the binder solution. This causes the granules to bind together, forming bridges between them. The fluid bed granulator allows for a controlled environment where the granulation process can be easily monitored and adjusted.
Why is milling necessary after granulation?
-Milling is necessary after granulation to break down large granules and create a standardized granule distribution. This ensures uniformity in the final product, which is important for consistent tablet weight and dissolution properties.
What is the purpose of adding a lubricant after the granulation process?
-The purpose of adding a lubricant after the granulation process is to coat the final granules. This coating allows the formulation to flow more easily through the tablet press, reducing friction and preventing the tablets from sticking to the press or each other.

Outlines

00:00

💊 Granulation in Tablet Formulation

This video by LFA discusses granulation, a critical process in tablet formulation. Granulation serves three main purposes: improving the flowability of the formulation, enhancing its compressibility, and ensuring a uniform distribution of the active pharmaceutical ingredient (API). The video introduces a method to test flowability by measuring the angle of incidence of the powder. A low angle indicates good flowability, suitable for direct compression, while a high angle suggests the need for granulation to prevent issues like arching or bridging during tableting. Direct compression is highlighted as a cost-efficient method when neither dry nor wet granulation is required, and it's particularly suitable for heat and moisture-sensitive APIs. The video also mentions the importance of mix validation to ensure proper blending of the formulation. Granulation techniques, both dry and wet, are explained, with dry granulation being preferred for formulations sensitive to moisture or heat. Wet granulation involves the use of a binder in a liquid solution to aggregate particles, and the video describes the process of fluid bed granulation, which includes spraying, wetting, and drying stages. After granulation, milling is necessary to standardize granule size, and lubricants are added to facilitate the flow of the formulation through the tablet press. The video concludes with a resource for recommended suppliers and further information.

Mindmap

Keywords

💡Granulation

Granulation is a pharmaceutical process used to create granules from powders. It is essential for improving the flowability and compressibility of formulations, ensuring a consistent distribution of active pharmaceutical ingredients (APIs). In the video, granulation is discussed as a critical step in tablet formulation, with both wet and dry methods being highlighted. The script mentions that granulation can help prevent issues like arching, bridging, or rat holing during tablet compression.

💡Flowability

Flowability refers to the ease with which a powder can flow. In the context of the video, good flowability is crucial for direct compression in tableting. The script explains that testing the angle of incidence can indicate flowability, with a smaller angle signifying better flow. This is important because poor flowability can lead to inconsistencies in the tableting process.

💡Compressibility

Compressibility is the ability of a material to be compressed into a solid form, such as a tablet. The video discusses how granulation can enhance the compressibility of a formulation, making it easier to produce consistent tablets. This is important because formulations that are not compressible enough may not form uniform tablets, affecting the dosage and efficacy of the medication.

💡Angle of Incidence

The angle of incidence is a measure used to test the flowability of a powder. As mentioned in the script, a small angle indicates good flowability, suitable for direct compression, while a high angle suggests the need for granulation due to poor flow. This concept is used to determine the appropriate processing method for a tablet formulation.

💡Direct Compression

Direct compression is a cost-efficient tableting process where a formulation is compressed into a tablet without prior granulation. The video explains that this method is suitable for formulations that are sensitive to heat and moisture. However, it also emphasizes the importance of mix validation to ensure the correct blending of the formulation.

💡Dry Granulation

Dry granulation is a method of creating granules without the use of a liquid. It is highlighted in the video as an option for formulations that are sensitive to moisture or heat. The script mentions slugging as an example of dry granulation, where large tablets are formed and then broken down into granules for final compression.

💡Wet Granulation

Wet granulation involves the use of a liquid, typically water or another suitable solvent, to bind powder particles together. The video describes wet granulation as a popular method due to its applicability to most formulations. It involves spraying a binder onto the powder, allowing the particles to aggregate and form granules with solid bridges.

💡Binder

A binder in granulation is an adhesive substance that helps particles stick together to form granules. The video mentions that in wet granulation, a binder is incorporated into the process, often in the form of a solution or suspension. The choice of binder and the liquid used can significantly impact the granulation process and the final product.

💡Fluid Bed Granulator

A fluid bed granulator is a type of equipment used for wet granulation. As described in the video, it operates by spraying a binder onto powder particles while hot air is blown through a bed of material, causing the particles to bind together. This method is one of the easiest forms of wet granulation as it occurs within the same unit.

💡Milling

Milling is the process of reducing the size of granules to achieve a standardized granule distribution. After granulation, whether wet or dry, milling is necessary to ensure uniformity in the granule size. The video script mentions that milling is a step that follows granulation to prepare the granules for the final blending and tablet compression.

💡Lubricant

A lubricant in pharmaceutical tableting is added to the granules to reduce friction during the compression process, ensuring smoother tablet formation. The video explains that lubricants are added after the milling process to coat the final granules, facilitating easier flow through the tablet press. This step is crucial for the successful production of tablets.

Highlights

Three main reasons for granulation: improving flowability, compressibility, and ensuring consistent API spread.

Testing flowability through angle of incidence measurement.

Direct compression as a cost-efficient process for sensitive APIs.

Importance of mix validation for correct API and excipient blending.

Granulation process overview, including wet and dry methods.

Dry granulation for formulations sensitive to moisture or heat.

Slugging as a method to form large tablets with varying weights.

Roller compaction as an alternative to granulation.

Wet granulation for most formulations using an adhesive or binder.

Fluid bed granulator as an easy form of wet granulation.

Process of wet granulation including spraying, wetting, and drying phases.

Milling as a necessary step after granulation to standardize granule distribution.

Final blend completion with the addition of lubricants for easier tablet pressing.

LFA's recommendation of suppliers for granulation equipment.

Visit www.imtcva.org for more information on granulation and related equipment.