Five key factors to consider when selecting a granulation ...

A global rise in increased specialty drug innovation, greater access to medicines in developing countries, and a boost in regulatory approvals within new markets have heightened the demand for complex pharmaceutical products. Research assembled by GlobalData indicates that the industry faces challenges such as escalating operational costs and growing requirements for sustainability. As a response, pharmaceutical companies are increasingly outsourcing their manufacturing processes to manage expenses and enhance profitability.

Granulation plays a vital role in the manufacturing process, which is crucial for producing pharmaceutical dosage forms like tablets and capsules by converting powders into free-flowing, homogeneous granules.

When it comes to the choice of granulation processes, the decision hinges on two major factors: the properties of the drug and excipients, and the efficiency of the process employed. Current granulation technologies encompass spray drying, roller compaction, high shear mixing, fluid bed granulation, and extrusion.

According to Michael Schupp, head of process engineering at Gerteis—a specialist in complex granulation processes—this industry has witnessed a substantial increase in production over the past decade. Gerteis has responded by developing innovative technologies aimed at improving manufacturing efficiency and reducing processing durations.

Schupp highlights that selecting the appropriate granulation process for a specific product involves understanding the pros and cons of each technique, particularly how suited they are to the unique characteristics of the drug. For instance, certain pharmaceuticals may be particularly sensitive to moisture.

To aid customers in making informed decisions, Schupp outlines his top five considerations essential for selecting the right granulation system for tablet production.

1. Choosing wet or dry granulation

The choice between wet and dry granulation is arguably the most significant consideration when evaluating granulation methods.

Wet granulation entails the introduction of a liquid binder to the powder mixture, followed by granulation and drying. This process is more complex, necessitating extra equipment and time, and is only viable for products not sensitive to moisture or heat.

Conversely, dry granulation manufacturers create granules without the use of liquid solvents or binders, compacting powdered materials through mechanical pressure. This method is particularly advantageous for moisture- and heat-sensitive products, as it forgoes the need for drying or heating processes.

Schupp notes that the trend towards dry granulation has increased significantly, primarily due to its cost-effectiveness and high-level containment capabilities (up to OEB level 5).

“The main advantages of dry granulation include eliminating the need to incorporate solvents or binders, as well as avoiding the heat application required for drying,” Schupp explains.

2. Reducing energy consumption

Streamlining manufacturing processes to be more efficient and environmentally friendly is a pivotal goal across the industry. Implementing optimized systems reduces resource consumption and lowers energy costs.

“In the case of dry granulation, we conserve energy since we do not have to undertake drying afterward—it's inherently a dry process,” Schupp explains, emphasizing resource and energy savings.

In addition, minimal use of binders or moisture contributes to resource conservation.

3. Inclined rollers improve processability

Schupp elaborates on how the configuration of rollers contributes another advantage to dry granulation.

He explains that "the compaction zone comprises two press rollers with a variable, controlled gap subjected to consistent force. The resulting product ribbon can be sizable, requiring regulated milling to achieve the desired particle size distribution (PSD).”

“If the rollers are positioned horizontally, handling a steady feed rate can be problematic, as material may fall out due to gravity,” he adds.

The incline alignment of the Gerteis rollers and feeding unit contrasts with many competitors' configurations and greatly enhances feeding consistency and draws capabilities.

“An inclined feeding screw prevents unregulated feed from dropping onto the rollers. This design provides high frictional forces to pull in materials efficiently without slippage, maintaining temperature control for sensitive products without additional cooling,” Schupp clarifies.

4. Continuous lines mean faster processing

One of the notable advantages of dry granulation compared to wet granulation is its faster processing time, owing to its continuous nature.

“We achieve shorter processing durations with dry granulation since wet granulation typically operates in batch mode, where the volume of product is limited per batch. In contrast, roller compaction facilitates a continuous operation, allowing us to enhance output merely by extending machine operation time,” Schupp explains.

Moreover, both Wash-in-Place and Clean-in-Place technologies significantly reduce cleaning-related downtimes.

5. Less equipment, more economical

Lastly, Schupp mentions that utilizing advanced equipment can lead to financial and spatial savings in the clean room environment. In essence, adopting a "less is more" philosophy with high-performance equipment minimizes the footprint, negating the requirement for additional cooling systems.

“Space in clean room production settings represents a significant cost. Therefore, the implementation of dry granulation can be economically advantageous due to the reduced area needed in processing zones,” he concludes.

For more insights on optimizing granulation processes, explore Granulation Series Exporter.