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 has allowed greater precision and reassurance throughout the pharma production processes, and while both wet and dry granulation techniques remain essentially the same, they’ve benefited greatly from scientific breakthroughs.
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
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 used widely by) today’s pharma industry. But increasingly, they represent challenges in terms of strict regulatory guidance and market competitiveness.
Why integrated granulation?
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 a lower overall cost.
It’s increasingly apparent that integrated granulation lines are better suited to dealing with such fine margins and big demands.
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
1. Optimum footprint – reduced space requirements/facility costs
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.
2. Contained product handling – improved industrial hygiene
For non-integrated granulation setups, materials need to move 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 the 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.
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. In addition, the closed-loop operation makes an integrated granulation system more secure and reliable.
3. Higher safety standards – for equipment, personnel, and premises
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. However, anything but the safest possible working environment across the granulation train is essential –not just in terms of operator safety but also for product integrity and potential damage to related equipment or even premises.
4. Common controls platform and integration of systems – hassle-free operation
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. 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.
5. Improved GMP compliance – ahead of the regulatory curve
Integrated granulation systems are more aligned with GMP guidelines, thanks to minimal manual intervention and reduced product exposure.
Granulation 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 a labour-intensive pharma operation – so an integrated system can overcome several of these challenges and boost efficiency, safety, and output. There are immense benefits that can be derived from the integrated granulation system, including creating a modernised manufacturing facility with innovative technology that supports compliance with current regulations, optimises operations, and reduces costs and risks. Plus, it provides enhanced manufacturing competitive advantages. Now, it is up to pharma manufacturers how they want to exploit this technology in the best interests of their business.