(203c) Understanding Critical Parameters in Roller Compaction Process and Development of a Novel Scaling Method

Roller compaction is a widely used size enlargement unit operation in many industries. In pharmaceutical industry, roller compaction has become the method of choice for dry granulation. While having all the benefits a granulation process can provide such as improving material flow behavior and content uniformity, roller compaction offers unique advantages over wet granulation for moisture, solvent or heat (drying) sensitive compounds. In roller compaction, powder is fed to two counter-rotating rolls which draw the powder between the rolls due to friction and compact the powder. Roller compaction is seemingly a simple process but the fundamental mechanisms are complex due to a number of material properties and machine variables involved such as material flow properties, friction against roll surface, compressibility, compactibility, elastic properties, air permeability, roll surface, roll dimension, roll pressure, roll gap, roll speed, feed method and conditions (gravity or screw, screw design, vacuum or not) and feed pressure. Only a handful of researchers have conducted analysis of the process at more fundamental levels, their findings, however, are not directly applicable to the practical roller compaction process development and scale-up. In practice, roller compaction formulation and process development still largely relies on experience, trial-and-error and DOE. There is an apparent need to develop roller compaction product process development and scale-up methodology that is based on fundamental understanding but is also applicable to actual practice. In this study, we examine the links between the consolidation mechanisms during roller compaction and the controllable parameters of a roller compactor.

There are generally three controllable parameters in the roller compaction process: roll pressure, roll gap (or, when without gap control, ribbon thickness that can be controlled by feed screw speed), and roll speed. Because the consolidation of a powder blend into ribbons is the result of mechanical stress (normal and shear stresses) within the powder during roller compaction, all the parameters are studied by examining their correlation to the normal (compressive) stress and the shear stress. To understand the impact of roll pressure, a novel approach was developed to establish the relationship between the roll pressure and the maximum normal (compressive) stress based on force equilibrium for any given roller compactor. The effect of roll gap was investigated by determining normal stress and shear stress as a function of roll gap. The influence of roll speed was examined through the strain rate of compression in roller compaction and the air entrapment effect. Based on the new understanding of these parameters, a novel scaling method for roller compaction process was developed and tested against an existing scaling method used in the industry.

In this study, the blends of 3:1 and 1:3 microcrystalline cellulose and lactose, respectively, lubricated with 0.5% magnesium stearate, were used as model materials to represent more ductile and more brittle formulations, respectively. They were roller compacted at a wide range of roll pressures and roll gaps on Alexanderwerk® WP120, Alexanderwerk® WP200 and a costumer-built instrumented roller compactor. The normal and shear stresses during the process at different conditions were measured via a roller instrumented with strain gages on roll surface across roll width. The density/porosity of ribbons was measured using an envelope density instrument called GeoPyc® 1360. The ribbons were milled by the WP120 RFG. The granules were characterized for particle size, bulk and tap density. They were then lubricated with 0.25% extra-granular and tested on a compaction simulator for compactibility assessment.

The results show that (1) higher roll pressure leads to higher normal and shear stresses, higher ribbon density, coarser granules, higher bulk and tap density and lower tablet tensile strength; (2) larger roll gap results in lower normal and shear stress, lower ribbon density, finer granules, lower bulk and tap density and higher tablet tensile strength; (3) roll speed has little or no effect on any characteristics of the ribbons and granules; (4) the commonly scaling method consistently leads to lower ribbon density, bulk and tap density, and higher tablet tensile strength when applied to scale-up. Conversely, it leads to higher ribbon density, bulk and tap density, and lower tensile strength when applied to scale-down. This demonstrates that for scale-up, the existing method underestimates the roll pressure needed at larger scale to generate similar stress. Conversely, for scale-down, it overestimates the roll pressure needed at small scale to generate similar stress; and (5) the proposed new scaling method has produced much similar ribbon density as well as bulk and tap density relative to the existing method and nearly identical tablet tensile strength between small and large scales for both scale-up and scale-down at all conditions.

From this study, it was concluded that (1) roll pressure is the most critical parameter in roller compaction process; (2) roll gap becomes an important parameter when significant change in roll gap occurs (e.g., > 1.5 mm); (3) roll speed has negligible impact on the process; (4) it is essential to establish the correlation between the roller compaction parameters and the normal and shear stress in order to enhance the understanding of the process and improve the process development and scale-up methodology; (5) the new scaling method based on relationship between roll pressure and maximum normal (compressive) stress and the effect of roll gap on the max stress is valid and that the new scaling method is clearly superior to the currently commonly used method.