High shear granulators (HSGs) are foundational to solid dosage manufacturing, widely used across development and commercial production. Yet despite their ubiquity, they’re often misunderstood. Misconceptions persist—some stemming from legacy experiences, others from misapplied process principles.
This article addresses six common myths surrounding HSGs and clarifies what modern pharmaceutical teams should truly understand when selecting or optimizing this granulation method.
1. “High Shear Granulators Always Cause Over-Wetting or Agglomeration”
While over-wetting is a legitimate risk in any wet granulation process, it’s rarely the fault of the equipment. Today’s HSGs offer tightly controlled binder spray systems, customizable impeller/chopper speeds, and in some cases, torque or endpoint monitoring.
Over-wetting typically results from poor process development or inadequate process monitoring. With real-time tools like torque sensing or in-line spectroscopy, modern HSGs can precisely detect granule growth and halt binder addition at the right endpoint.
2. “You Can’t Use HSG for Moisture-Sensitive APIs”
While HSG often involves water-based granulation, it is by no means limited to aqueous systems. Many manufacturers use alcohol-based binders or minimal-moisture formulations with optimized spray control. In well-designed systems, exposure time to moisture is brief, and granule drying begins almost immediately.
Formulators working with humidity-sensitive APIs have successfully used isopropanol-based binders and optimized process controls to manage impurity levels and stability—proving that HSG can be viable even for sensitive actives.
3. “Fluid Bed Granulation Is Always Better”
Fluid bed granulation (FBG) is advantageous in some contexts, particularly when integrating drying and granulation in a single unit. However, HSG has its own merits. These include shorter batch times, higher bulk density granules, and reduced fines.
In situations requiring high drug load, improved compressibility, or controlled particle size distribution, HSG is often the preferred method. It also generally requires a smaller equipment footprint and offers better process containment for potent APIs.
4. “High Shear Granulation Is Hard to Scale Up”
Scaling HSG is more technical than difficult. When done correctly, it follows well-established principles: maintaining geometric similarity, controlling impeller tip speed, adjusting binder spray rate relative to batch size, and using a consistent fill ratio.
Modern scale-down and scale-up tools—including miniaturized pilot-scale HSGs and computational modeling—enable efficient tech transfer. Design of Experiments (DoE) and process analytical technologies (PAT) further streamline the process.
5. “HSGs Are Energy-Hungry and Hard to Maintain”
Earlier models may have had high energy demands and difficult cleaning protocols, but current HSGs have evolved significantly. Newer systems come with variable frequency drives, CIP/SIP compatibility, and modular construction for fast cleaning and maintenance.
Equipment design now routinely considers cleanroom ergonomics, operator safety, and preventive maintenance. As a result, downtime and total cost of ownership are significantly reduced.
6. “Twin Screw or Low Shear Granulation Always Delivers Better Granules”
Granule quality is highly formulation-dependent. HSG tends to produce granules with higher density, superior flowability, and narrower particle size distribution—all desirable for direct compression and high-speed tableting.
Twin screw or low shear methods may be preferable in continuous or sensitive processing applications, but for batch processes requiring robust granules and minimal fines, HSG remains highly effective.
Summary
High shear granulation remains one of the most versatile and reliable techniques for solid dose manufacturing. Its reputation suffers more from historical bias and limited exposure than from technical limitations.
Pharmaceutical manufacturers looking to optimize process efficiency, scale-up strategy, or formulation robustness would benefit from revisiting HSG with modern tools and a fresh perspective. The opportunities for efficiency and control are often far greater than perceived.
