(203d) Minimization of Roller Compacted Ribbon Density Gradients through Modified Roll Design

The practice of dry granulation via roller compaction is frequently used in the pharmaceutical industry to enhance the flow and processing properties of fine powder blends. This process presents an alternative for particle size enlargement of compounds that due to stability concerns cannot be wet granulated. The fact that roller compaction offers relatively high throughput capacity is another driver behind this operation's increasing prevalence.

Characterization of numerous roller compacted products has revealed that significant density gradient across the compacted ribbon widths, where the edges are lower in density relative to the center, appear to be an inherent product property. This is believed to be due to the combined effect of non-uniform powder feed into the compaction zone as well as material drag leading up to and within the compaction zone. Studies revealed that the density gradients can ultimately contribute to fines generation and bi-modal particle size distributions of the final milled product. Further studies indicate that excessive work hardening of plastically deforming excipients at the center of a ribbon can lead to reduced granule compactibility and result in lower final compressed tablet hardness values.

In this investigation, roller compaction trials examined the effect of material properties on the ribbon density gradients by utilizing three very different formulations. These included a lactose based placebo, a dicalcium phosphate based placebo, and a formulation comprised of 30 percent by weight of a fine, poorly flowing API. Various lubricant and glidant levels were also evaluated within each of the three base formulations. The impact of process parameters including the roll gap and hydraulic pressure on the resulting ribbon density distributions was also evaluated. Several new sets of rolls were then designed and fabricated in an attempt to eliminate the ribbon density gradients. The design involved a modified approach to interlocking rolls, with the roll surface contoured to match the measured ribbon density gradients. The primary purpose of the contour was to accommodate the lower level of powder believed to be fed to the ribbon edges.

Results for the formulations studied showed that material properties did not largely change the density distributions across the ribbon widths. While roll pressure had little impact on the density distributions, the roll gap appeared to have an effect. Higher gaps resulted in more uniform density distributions, though lower average densities. Trials with modified rolls were able to achieve nearly uniform density gradients with narrower pore size distributions across the ribbon widths. Successive processing steps revealed that the modified rolls contributed to a modest reduction in fines content after milling and an increase in compressed tablet hardness values. The trials did not indicate any detrimental effects on material properties from implementing the modified rolls.