integrated granulation - a step towards smart pharma ... · an integrated granulation system is a...
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Integrated Granulation - A Step towards Smart Pharma Operations
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Granulation is central to pharmaceutical manufacturing. High-quality, free-flowing granules not only form tablets of excellent quality but also ensure the desired disintegration time and subsequent dissolution profile – thereby ensuring accurate dosage delivery.
Continuously advancing technology allows greater precision and reassurance throughout production processes, and while both wet and dry granulation techniques remain essentially the same, they’ve benefited greatly from scientific breakthroughs.
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Wet granulation– an industry cornerstone
Despite being a complex, time-consuming, and typically labour-intensive operation involving multiple processes and equipment, wet granulation remains the most popular approach. Today, it accounts for more than 85% of the global industry’s granulation output.
Here are just a few reasons why:
• Improved/better-moderated dissolution rates, which enhance the release and bioavailability of less soluble drugs
• Ensures content uniformity in tablets
• Increases formulations’ average particle size
• Enhances powder’s flow properties
• Improves compressibility
For low-dose drugs, wet granulation is indispensable – significantly improving content uniformity of tablets with less than 20 mg API.
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Wet granulation techniques have diversified in parallel with technological advances. For example, the types of binder used, and the methods used in applying them, continue to evolve – yet conventional wet granulation remains pharma manufacturers’ enduring preference.
Of course, conventional wet granulation methods remain well adapted to (and use widely by) today’s pharma industry. But increasingly, they represent challenges in terms of strict regulatory guidance and market competitiveness.
And increasingly, integrated granulation is the solution…
Today’s most common wet granulation techniques
Conventional wet granulation suite: RMG + FBD + Milling + Blending
RMG FBD
Wetgranulation
Conventionalgranulation
Fluid bedgranulation
Dry milling Seiving Blending
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Why integrated granulation?
Technological innovation and stricter regulatory compliance are changing the pharma manufacturing landscape significantly, and faster than ever. At the same time, governmental policy all over the world demands cheaper drugs, while the FDA insists – quite rightly – on higher quality standards. All this positive progress has forced pharma manufacturers to reassess and revise existing manufacturing processes.
A conventional granulation setup is flexible to a point, but by design, it involves standalone, multiple-step operations. What’s more, it presents many challenges at the material-handling level, including:
• The need for significant production space
• A typical lack of product containment
• Poor industrial hygiene
• Labour-intensity and multiple operators
• Longer processing times
• Lower yield due to loss at material transfer points
• Higher product contamination risk
• Injury risk to operating personnel
• Increasing pressures through Good Manufacturing Practices (GMP) compliance
• The cost and time for cleaning and validating each piece of equipment.
Hence there’s a pressing need for new manufacturing concepts that can produce pharmaceuticals of exceptional quality, within tighter timelines, at lower overall cost.
It’s increasingly apparent that integrated granulation lines are better suited to dealing with such fine margins and big demands.
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Batch-type wet granulation, using a high-shear mixer (HSM) and a fluid bed dryer (FBD), is the most commonly used technique in pharma manufacturing. An integrated granulation suite combines HSM and FBD operations, along with milling, to achieve closed-loop continuous processing and reduce interruption. Integrating the equipment doesn’t change the basic principles of the wet granulation process – instead, it enhances overall process efficiency while reducing the associated challenges.
Benefits of an integrated granulation line:
• Optimum footprint – reduced space requirements/facility costs
• Contained product handling – improved industrial hygiene
• Higher safety standards – across equipment, personnel, and premises
• Common controls platform and integration of systems – hassle-free operation
• Improved GMP compliance – ahead of the regulatory curve
Conventional granulation trains include several standalone components, requiring significant floor space. In contrast, an integrated solution not only reduces equipment’s overall footprint, but also cuts operational downtime through decreased cleaning and changeover time between the products, and reduces HVAC load.
Optimum footprint – reduced space requirements/facility costs
Being a compact system, GT X.ONE reduces floorspace requirements by around 50%. Furthermore, its through-the-wall construction allows clear separation between processing and technical areas, ensuring easier maintenance, cleaning and operation.
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For non-integrated granulation setups, materials need moving several times during the process. It starts from the charging of powders in the HSM for granulation, and continues with the transfer of wet granules to the wet mill, onto drying in the FBD, to the dry mill, and finally to the bin or blender.
During these transfers, the product is exposed to the ‘open air’ and operators. Steps such as the loading of dry powders into the HSM, and the transfer of dried granules to dry mill and blender, can generate a lot of potentially toxic dust. An integrated granulation train is therefore designed to ensure containment of product dust and vapours during transfers, and this is especially crucial for processes involving organic solvents and moisture-sensitive products. Meanwhile, a closed-container operation prevents potential product contamination and reinforces safety for operating personnel.
GT X.ONE eliminates open product transfer points by ensuring safe and smooth material flow through carefully engineered large-diameter pipes. A vacuum charging system provides closed-loop material transfer, and so vastly reduces dust generation and product exposure. Granule sizing is made easier by integrating mill equipment into the system.
Vacuum charging of materials HSM wet mill fluid bed dryer dry mill bin/blender
Contained product handling – improved industrial hygiene
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Loading and unloading materials during granulation typically involve significant manual labour in a noisy and potentially dangerous environment. But an integrated granulation system simplifies the process in several ways, and in doing so, makes it safer. For example, during material charging and discharging, the HSM remains closed, which eliminates operator exposure to toxic dust and vapour. Closed-loop operation makes an integrated granulation system more secure and reliable.
Thanks to wider charge points, GT X.ONE is easier and more flexible to use. Options allow for vertical or horizontal charging, and gravity or vacuum-assisted material flow. The mixer features WIP-ready integrated cleaning nozzles for product bowl and discharge. Even the fluid bed system is equipped with a tangential charge port, ensuring safe and efficient product transfer – and the entire piping system is sloped to one central drain, providing full WIP capability, while the impeller lifting system allows easy inspection and verification.
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An integrated granulation system is a huge investment for pharma companies, and safety is a primary consideration when choosing a supplier – so suitable vendors must design and build granulation equipment with equivalent care and attention to detail.
Anything but the safest possible working environment across the granulation train simply isn’t enough – and not just in terms of operator safety, but also for product integrity and potential damage to related equipment or even premises.
Higher safety standards – for equipment, personnel, and premises
Utmost safety is one of the key benefits of GT X.ONE, and it features the Maximum Operational Safety Technology (MOST) concept, certified by independent European authorities.
The FBD features ACG’s X.ONE technology, which is guaranteed to withstand pressures of up to 12 bar, and designed to withstand higher.
What’s more, the system is equipped to handle aqueous and organic solvents, and its 12 bar-rated inflatable seals feature machined C-flanges that also ensure safety at low pressure - even at less than 4 bar.
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A truly integrated granulation system has a single PC-based common control platform, rather than each piece of standalone equipment having its own electronic control panel attached to the part of the train it relates to. GT X.ONE’s integrated control interface is an Ethernet-based system that reduces installation labour and controls not only each piece of the system but also the system as a whole.
This ensures the interlocks between the granulation train’s major operational components are in place, and that batch data can be uploaded automatically for faster overview and analysis.
Common controls platformand integration of systems – hassle-free operation
The control platform of GT X.ONE includes ACG X.ONE Command — an advanced technology for intuitive and secure monitoring and control of GT X.ONE. It features:
• A PC-based control system with COPA-DATA Zenon software with modular programming
• CE, FDA, ATEX, ISA-88, GAMP 5, and 21 CFR Part 11 compliance
• Interfaces to MES, ERP, local networks or databases for long-term process documentation
• Enhanced data integrity
• Use of master and control recipes
• Chronological Event List (CEL) and alarm administration module for US Food and Drug Administration (FDA)-compliant auditing
• A Matrix Recipe Editor to enable personnel without automation experience to control processes more easily
• Validation based on GAMP lifecycle concept
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Integrated granulation systems such as GT X.ONE are more aligned with GMP guidelines, thanks to minimal manual intervention and reduced product exposure.
Improved GMP compliance – ahead of the regulatory curve
GT X.ONE is an ideal integrated granulation train for alignment with GMP practices. Its features include a compact footprint, through-the-wall construction, minimal human intervention, closed-loop processes, easy cleaning procedures, and automated, audit-friendly control systems.
One of the most significant considerations behind the design of GT X.ONE – alongside operational efficiency and integration – is operator comfort and protection. Processes are intuitive and hassle-free, and the combination of ergonomics and safety is evident in every aspect of the system.
Designed to perfection
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Product bowl
GT X.ONE’s HSM is designed to ensure operators’ easy access without unnecessary physical effort. The bowl can be free-standing position or ‘through-the-wall’, depending on floor space and configuration, and is equipped with an easy-access platform for easy charge and discharge of materials.
Unique Z-shaped impeller
The HSM is equipped with a Z-shaped impeller to ensure the optimum flow of material in and out of the shear zone. It also provides superior centrifugal force to the material than conventional systems, minimises material sticking to the bowl surface, and consumes significantly less power.
Knife-edged multi-blade chopper
A multi-blade chopper inside the bowl breaks down lumps formed during granule formation, avoids ‘dead zones’, and achieves uniform binder distribution when applied to powders. It ensures highly effective chopping even at lower speeds and reduces stress on the product through greater efficiency.
Product bowl
Chopper
Impeller
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Blow-back filter assembly
During dry mixing of low bulk density API, powder tends to flow out, and this can cause batch rejection and non-uniformity of content. HSM X.ONE’s blow-back filters ensure this doesn’t happen, thanks to 5-micron blow-back filters on the inside of the HSM lid, keeping contents securely inside, and cyclically purging the trapped powder into the bowl.
Spraying manifold
The spraying manifold/nozzle distributes the binding agent without additional air, ensuring uniform application.
Non-continuous mode of discharge
Once the wet mix is complete, a non-continuous impeller ‘on-off’ jog controls discharge.
Chamber pressure sensor
Precise pressure measurement inside the bowl to ensure safe operation.
The built-in blow-back filter system
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Accurate and easy endpoint determination
Torque-based measurement determines the precise endpoint of wet granulation in the HSM and is more sensitive and accurate than time- or current-based measurements.
MOST safety concept
The fluid bed processor is equipped with the revolutionary MOST safety technology, ensuring:
• No mechanical deformation caused by an explosion, thanks to flexible cross-support
• Zero environmental impact, achieved with a non-vented, fully contained design
• Absolute investment in peace of mind
Multi-function column (MFC)
The fully integrated multi-function column of GT X.ONE saves maintenance time as well as money. The smart, open-profile column has hand-removable covers for swift and simple access to integrated peripherals, while a linear drive makes raising and lowering the exhaust air filter far easier. The control panel and keyboard are adjustable to operator preference.
Ergonomic product container
Twin bull-eye windows allow improved inspection of granules as they dry in the FBD, and a side-discharge port is attached at the bottom. The height of the product container is adjustable for easier, safer attachment.
Directional flow plate
Fixed at the bottom of the product bowl, the directional flow plate ensures 99% efficiency in side-discharging the product. The plate is also designed to ensure hot air has a spiral flow for greater force, which means faster drying and more spherical granules of higher density.
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Explosion-proof plenum
The lower plenum of FBE X.ONE is fully shock absorbent for comprehensive protection against explosion.
Ergonomic, safe and efficient product transfer… and cleaning
A specially designed compressed air system targets the HSM’s discharge valve seal for enhanced safety, product quality, and cleanability, while the tangential charge port ensures higher efficiency in product transfer.
Shaking filters
Equipped with shaking filters instead of blow-back ones, the fluid bed system not only prevents powders from escaping to the environment but also returns powders fluidised during the drying process to the powder bed. This is particularly advantageous when dealing with products that have high moisture content.
Purging air inlet
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Start as you mean to go onGranulation is the crucial first step in creating a robust solid dosage form. It lays the foundation for top-quality tablets and capsules and also defines their dissolution characteristics and subsequent therapeutic efficacy.
However, granulation is a fine-margin exercise and can be labour intensive pharma operations – so an integrated system can overcome several challenges and boost efficiency, safety, and output.
GT X.ONE is ACG’s response to a long-standing need for greater flexibility and reassurance across the granulation line. It makes granulation more adaptable and seamless, and enhances aesthetics, safety, and output.
It’s literally a shining example of how collaboration and applied insight can ensure less waste and downtime, while improving product consistency and quality – all in one advanced and ergonomically informed user experience.
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