Roller compaction process factors

As shown in Figure 27, it is apparent that when the roller compaction force was scaled-up, the compactibility curve of the tablets shifted downward. Ideally, a formulator would prefer a 60 N hardness window of acceptable force. In this example, the flat part of the curve had no effect on friability and dissolution and thus could be processed. The example does show that for a roller compaction process, a scale-up factor must be considered for the roller compaction force early on in development. Factors that affect the tablet compactibility curve at scale-up include the roller compaction force and strain-rate sensitivity of the compact. 

One factor that may contribute to the nonuniformity of strain is an increase in roller speed. During the main stage of the compaction process, the strain rate in volume elements varies from point to point in a cup and with cup position. In the simplest geometric estimation of these strains, their rates of change will be directly proportional to roller speed. Some of the interrelated effects resulting from an increase in roller speed are (or may be) ... 

In contrast, increasing the gap width between the dry granulator rollers decreases the density of the compacted ribbon or briquette (also possible when other factors, such as feed rate or roll force, are changed). This reduced densification process results in a weaker binding of API to carrier excipients, and reduced overall granulation particle size distribution and increased bypass. 

Another scale-up approach, which is simple to understand, is to scale-up the compaction force based on the roller width. In this approach, once the desired tablet characteristics (i.e., tablet dissolution, granule flow, minimal tablet weigh variation, tablet hardness, and minimal tablet friability) are obtained, the ribbon compaction force is noted during processing from the known roll width. As the product is scaled up, the applied force is scaled up based on the roller width. Table 5 provides several examples of scale-up factors that can be used as a guide. This technique has been found to be successful, but may have some limitations as the entire scale-up relationship may not be linear. 

As reported earlier, compaction simulators can be equipped to replicate the compression process of a roller compactor. Zinchuk et al. describe how a compaction simulator can be used to produce ribbons and determine the formulation specific compactability relationship (tensile strength vs. solid fraction) (Fig. 27) (4), Since compacts produced under equivalent stress-strain conditions exhibit similar mechanical properties, the ribbon solid fraction and/or tensile strength can be used as a scale-up factor for pilot and eventually commercial scale manufacturing. 

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