David O’Connell of PCI Pharma Services explores the advancements in dry granulation and the fundamentals of roller compaction, presenting it as a viable alternative to traditional wet granulation for producing oral solid dosage forms like tablets and capsules.
Q: What exactly is roller compaction?
A: Roller compaction is a crucial process in the pharmaceutical industry, particularly in the formulation of solid dosage forms. This dry granulation technique involves the aggregation and densification of dry powders components into a uniform solid mass, known as a ribbon, which is subsequently broken down into specific granule sizes via a milling system. In this process, powder particles adhere to one another, forming larger compacts, without the addition of a liquid binder, distinguishing it from wet granulation methods such as high shear or fluid bed granulation. Essentially, dry granulation compacts a powder blend by applying force, increasing the density, preventing powder segregation, improving compaction and flow properties of the resulting granules.
Q: So how does this form of dry granulation work?
A: In roller compaction, a powder blend is fed, either by gravity or through a feeding system (auger feeder and tamp auger), into a set of directly opposed rotating rollers. The powder is then introduced into a narrowing gap between the rollers, where it subjected to high pressure. This pressure increases the bulk density and particle size uniformity of the granules. The primary goal of dry granulation is to enhance the bulk density of powders and improve particle size uniformity to ensure better flow properties, which is crucial for high-speed tablet and capsule manufacturing.
Q: Can you provide a little more detail?
A: The roller compaction process begins with feeding the powder blend into the rollers. The gap between these rollers is carefully controlled, and the powder is subjected to high pressure and a specific roller speed. This compaction forces the powder to form a dense ribbon. The pressure applied, roller speed and the gap dimensions are the most critical parameters, as they directly influence the bulk density and uniformity of the resulting granules. Precise control of these parameters is essential to ensure consistent granule properties, which are vital for downstream processing into dosage forms like tablets and capsules.
Q: Why is the pressure or force applied so important?
A: The pressure applied during roller compaction is crucial because it determines the degree of densification and compaction of the powder blend. The applied pressure compacts the powder into a ribbon with predetermined thickness. The required pressure depends on the material, process parameters and product specification. This defined pressure must be carefully controlled to ensure uniformity in the ribbon and the resulting granules. Variations in the applied force can lead to inconsistencies in granule density and particle size distribution, affecting the overall quality and performance of the final dosage form.
Q: Does roller compaction offer any benefits over wet granulation?
A: Roller compaction offers several advantages over wet granulation, particularly for moisture-sensitive compounds. Unlike wet granulation, roller compaction does not require the addition of an aqueous solvent to aid in the binding of primary formulation components, making it suitable for compounds that may degrade or form toxic impurities when exposed to moisture. Additionally, roller compaction eliminates the need for a drying stage, making it ideal for heat-sensitive compounds. This results in a more efficient process with shorter production times. Moreover, roller compaction can support continuous batch processing, enhancing overall production efficiency and reducing operational costs.
Q: Do other forms of dry granulation exist?
A: Yes, another method of dry granulation is slugging. In slugging, a tablet press compacts the powder into large tablet compacts, or “slugs,” using large flat tooling. The resulting slugs are then milled into granules using an oscillating or conical mill. However, slugging presents several challenges. The pre-slugged blend does not consistently fill into the tablet die (poorly flowing materials with low bulk density materials), leading to inconsistencies in tablet weight and compaction force. These variations can cause differences in the mechanical strength of the slugs, resulting in differential granulate production. Due to these challenges, slugging is less commonly used, with roller compaction being the preferred method for dry granulation.
Q: Do different types of roller compaction exist?
A: Yes, there are two primary types of roller compaction systems: fixed rolls and floating rolls. In fixed roll systems, the distance between the rollers remains constant, which can lead to inconsistencies in the compaction force if the powder feed varies. In floating roll systems, the gap adjusts dynamically based on the amount of powder being fed, maintaining consistent compaction force and resulting in more uniform granules.
Q: Does one offer any advantage over the other?
A: Floating roll systems are generally considered superior due to their ability to adjust the roller gap based on powder feed, maintaining consistent compaction force. This minimizes fluctuations in ribbon thickness and granule properties, leading to a more homogeneous granulate. Technologies like GERTEIS® employ this floating gap system, providing better control and uniformity in the granulation process, ensuring high- quality and consistent granules suitable for further processing.
Q: After compaction, what happens next?
A: Following compaction, the resulting ribbons are milled into granules using a screen with a specific mesh size to control particle size. Depending on the type of roller compactor the milling system can be online or performed off line. The milling should be gentle to avoid generating fines, which can negatively impact granulate quality and therefore oscillating millings are commonly used, rather than conical mills. The granules produced through roller compaction are then processed to extra-granular blending (additional excipients i.e. diluent disintegrants and lubricants) and then onto into tablets or capsules or bottle/sachet filling, ensuring dose uniformity and improving product consistency. This continuous process ensures efficiency and high throughput, essential for large-scale pharmaceutical manufacturing.
Q: How does roller compaction fit into the development of specialized medicines, such as those with increasing potency?
A: The development of highly potent compounds requires specialized handling to ensure safety and efficacy. Traditional reliance on personal protective equipment (PPE) is being supplemented with
contained engineering solutions to enhance operator protection. CDMOs must incorporate fully contained roller compaction systems capable of processing potent molecules with occupational exposure limits (OEL) as low as 0.01 μg/m3. At PCI Pharma Services, for example, we have invested in state-of-the-art contained roller compaction facilities to address the growing demand for processing highly potent compounds. This ensures we can offer both wet and dry granulation solutions while maintaining the highest safety standards.
Q: How has PCI Pharma Services responded to the increasing demand for dry granulation of potent molecules?
A: PCI Pharma Services recognized the need for specialized facilities to handle potent compounds and invested in a fully contained roller compaction solution within our purpose-built manufacturing facility. This investment allows us to process potent molecules with low OELs without relying solely on PPE. Our facility’s design ensures that we can handle both dry and wet granulation with best-in-class containment, offering our clients comprehensive solutions for the development and manufacture of highly potent drug products.
By leveraging cutting-edge technologies and maintaining stringent safety and quality standards, PCI Pharma Services continues to lead in the development and manufacturing of oral liquid dosage forms, ensuring that we meet the evolving needs of the pharmaceutical industry.
Q: What future trends do you see in the roller compaction process?
A: The future of roller compaction in pharmaceutical manufacturing looks promising with advancements
in technology and a growing focus on specialized medicines. We anticipate continued improvements
in roller compaction equipment, including more sophisticated control systems that enhance precision and uniformity. Additionally, the integration of real-time monitoring and process analytical technology (PAT) will further optimize the roller compaction process, ensuring consistent quality and reducing the risk of deviations.
Q: How is the industry addressing the need for continuous processing?
A: The pharmaceutical industry is increasingly adopting continuous processing to improve efficiency and scalability. Roller compaction is well-suited for continuous processing due to its ability to provide consistent granules in a streamlined manner. By integrating roller compaction into continuous manufacturing lines, companies can achieve higher throughput, reduced downtime, and lower production costs. This shift towards continuous processing aligns with the industry’s goal of enhancing manufacturing efficiency and flexibility.
Q: What role does sustainability play in roller compaction?
A: Sustainability is becoming a key consideration in pharmaceutical manufacturing. Roller compaction supports sustainability by eliminating the need for solvents and reducing energy consumption associated with drying processes. The ability to process heat- and moisture-sensitive compounds without additional energy-intensive steps contributes to a greener manufacturing process. Furthermore, advancements in roller compaction technology aim to minimize waste and optimize resource utilization, aligning with the industry’s sustainability goals.
Q: How is PCI Pharma Services positioning itself for the future?
A: PCI Pharma Services is committed to staying at the forefront of pharmaceutical manufacturing by continually investing in advanced technologies and infrastructure. We focus on developing innovative solutions that meet the evolving needs of our clients. Our state-of-the-art facilities and commitment to quality and regulatory compliance ensure that we remain a trusted partner for pharmaceutical companies worldwide. As the industry advances, we will continue to leverage our expertise and capabilities to deliver high-quality, efficient, and sustainable manufacturing solutions.
Conclusion
Roller compaction is a critical process in pharmaceutical manufacturing, offering numerous benefits, especially for moisture- and heat-sensitive compounds. With advancements in technology and a growing focus on specialized medicines, roller compaction is poised to play an even more significant role in the future. PCI Pharma Services, with its state-of-the-art facilities and commitment to quality, is well-positioned to lead in this evolving landscape, providing comprehensive solutions for the development and manufacturing of high-quality pharmaceuticals and delivering life changing therapies to patients.
Author: David O’Connell, Director Scientific Affairs
David O’Connell is the Director of Scientific Affairs at PCI Pharma Services. After graduating from Glasgow Caledonian University with a BSc. in Applied Bioscience, David spent seven years as a Supervisory Scientist working for Aptuit in Edinburgh before moving to Penn Pharma as Head of Formulation Development in 2009. Here he played a vital part in the design of the potent Contained Manufacturing Facility (CMF), which won the ISPE Facility of the Year award for Facility Integration (2014). In 2013 David took on the role of Director, Pharmaceutical Development at the PCI site in Tredegar and in 2017 became PCIs Director of Scientific Affairs.
Understanding Roller Compaction in Pharmaceutical Development with David O’Connell | As seen in IBI Magazine | July 2024.
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