Category: Manufacturing and Bioprocessing
Purpose: Conical milling is a commonly used granule size reduction or calibration technique in the pharmaceutical industry to increase surface area and thus improve the bulk density, powder flow and tablet compressibility properties of oral solid dosage (OSD) formulations. Some of the disadvantages of a milling process are the potential for the generation of unwanted heat, too many fines and wide particle size distribution curves resulting in variations in granule properties and final particle sizes. This disadvantage is further compounded when the material has a starting low bulk density. The purpose of this study was to evaluate a new impeller design, comprised of a full-face, forward-angled arm profile, to optimize downward air flow to improve material flow through the mill and reduce PSD variances in milled granules.
Methods: First, Computational Fluid Dynamics (CFD) analysis was performed to determine the anticipated theoretical air flow as a correlation to downward pressure exerted on powders and as an indicator of potentially improved milling performance between new impeller proposed and traditional conical mill impellers. Second, materials evaluated for this milling study composed of two placebo pharmaceutical formulations, Lactose and Oat Flour. These products were evaluated to understand the effects of varying physical properties (i.e. flow-ability, starting bulk density, incoming particle size, etc.) on final particle size distributions. Empirical milling was performed on a conical mill where the effects of a new impeller with full-face, forward-angled arms, were evaluated on the amount of back-pressure induced within the mill, percentage of fines generated and PSD curve variations vs. industry standard impeller profiles. DoE milling was performed with varying screens and RPMs.
Results: CFD analysis of the new full-face, forward-angled impeller arm profile selected showed an impact on the air flow pattern within the milling chamber. DoE results correlated the impact on the fines generated during milling with all four materials processed when compared to more traditional impeller profiles. It was observed with both CFD and DoE that the reduction of fines generated was closely related to the incoming material's bulk density and particle size. Furthermore, during the DoE, the new impeller arm profile affected product throughput without generating excessive heat or additional back-pressure within the milling chamber. Other variables such as impeller rotational speeds had minor effects on final PSDs at lower impeller RPMs, but the effectiveness of the new full-face, forward-angled impeller diminished as RPMs were increased.
Conclusion: In this Study, product flow and particle size variations in a conically milled product were improved through the optimization offered by the new full-face, forward-angled arms impeller. Selection of the impeller markedly affected the amount of fines generated during milling at lower RPMs. Optimization of the milling conditions resulted in a narrower particle size distribution of the granules, reduced fines, lower temperatures and higher capacities. Overall, this study design provided an approach to minimize fine generation potential for dry granulated products.